bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Data from CD36 drives metastasis and relapse in acute myeloid leukemia
Authors: Farge Thomas , Nakhle Jean , Lagarde Damien , Cognet Guillaume , Polley Nathaniel , Castellano Remy , Nicolau Marie-Laure , Bosc Claudie , Sabatier Marie , Sahal Ambrine , Saland Estelle , Jeanson Yannick , Guiraud Nathan , Boet Emeline , Bergoglio Camille , Gotanègre Mathilde , Mouchel Pierre-Luc , Stuani Lucille , Larrue Clement , Sallese Marie , De Mas Véronique , Moro Cédric , Dray Cedric , Collette Yves , Raymond-Letron Isabelle , Ader Isabelle , Recher Christian , Sarry Jean-Emmanuel , Cabon Florence , Vergez Francois , Carriere Audrey
Published: September 2024

Figure S1
Supplementary Video 1 from Targeting CaMKK2 inhibits actin cytoskeletal assembly to suppress cancer metastasis
Authors: Mukherjee Debarati , Previs Rebecca A. , Haines Corinne , Al Abo Muthana , Juras Patrick K. , Strickland Kyle C. , Chakraborty Binita , Artham Sandeep , Whitaker Regina S. , Hebert Katherine , Fontenot Jake , Patierno Steven R. , Freedman Jennifer A. , Lau Frank H. , Burow Matthew E. , Chang Ching-Yi , McDonnell Donald P.
Published: September 2024

Supplementary Video 1
Table S1 from Mesenchymal-like tumor cells and myofibroblastic cancer-associated fibroblasts are associated with progression and immunotherapy response of clear-cell renal cell carcinoma
Authors: Davidson Guillaume , Helleux Alexandra , Vano Yann A. , Lindner Véronique , Fattori Antonin , Cerciat Marie , Elaidi Reza Thierry. , Verkarre Virginie , Sun Cheng-Ming , Chevreau Christine , Bennamoun Mostefa , Lang Hervé , Tricard Thibault , Fridman Wolf Herman. , Sautes-Fridman Catherine , Su Xiaoping , Plassard Damien , Keime Celine , Thibault-Carpentier Christelle , Barthélémy Philippe , Oudard Stéphane Marie. , Davidson Irwin , Malouf Gabriel G.
Published: September 2024

General and specific markers for the identification of each sub-cluster in scRNAseq analysis and associated references.
Table S1 from Activation of the cGAS/STING axis in genome-damaged hematopoietic cells does not impact blood cell formation or leukemogenesis
Authors: Dressel Nicole , Natusch Loreen , Munz Clara M. , Costas Ramon Santiago , Morcos Mina N.F. , Loff Anja , Hiller Björn , Haase Christa , Schulze Livia , Müller Patrick , Lesche Mathias , Dahl Andreas , Luksch Hella , Roesen-Wolff Angela , Roers Axel , Behrendt Rayk , Gerbaulet Alexander
Published: September 2024

List of antibodies used in the study
Supplementary Table 2 from Apolipoprotein E2 Stimulates Protein Synthesis and Promotes Melanoma Progression
Authors: Adaku Nneoma , Ostendorf Benjamin N. , Mei Wenbin , Tavazoie Sohail F.
Published: September 2024

Full GSEA results tail vein injection
Supplementary Table 1 from Apolipoprotein E2 Stimulates Protein Synthesis and Promotes Melanoma Progression
Authors: Adaku Nneoma , Ostendorf Benjamin N. , Mei Wenbin , Tavazoie Sohail F.
Published: September 2024

Full GSEA results BPC tumors
Supplementary Figures from Apolipoprotein E2 Stimulates Protein Synthesis and Promotes Melanoma Progression
Authors: Adaku Nneoma , Ostendorf Benjamin N. , Mei Wenbin , Tavazoie Sohail F.
Published: September 2024

Supplementary Figures S1 to S5
Table S3 from Dual inhibition of KRASG12D and pan-ERBB is synergistic in pancreatic ductal adenocarcinoma
Authors: Gulay Kevin Christian Montecillo. , Zhang Xinlian , Pantazopoulou Vasiliki , Patel Jay , Esparza Edgar , Pran Babu Deepa Sheik. , Ogawa Satoshi , Weitz Jonathan , Ng Isabella , Mose Evangeline S. , Pu Minya , Engle Dannielle D. , Lowy Andrew M. , Tiriac Hervé
Published: September 2024

Table S3. Results of RPPA and transcriptomic analyses.
Table S2 from Dual inhibition of KRASG12D and pan-ERBB is synergistic in pancreatic ductal adenocarcinoma
Authors: Gulay Kevin Christian Montecillo. , Zhang Xinlian , Pantazopoulou Vasiliki , Patel Jay , Esparza Edgar , Pran Babu Deepa Sheik. , Ogawa Satoshi , Weitz Jonathan , Ng Isabella , Mose Evangeline S. , Pu Minya , Engle Dannielle D. , Lowy Andrew M. , Tiriac Hervé
Published: September 2024

Table S2. List of antibodies used in this study.
Table S1 from Dual inhibition of KRASG12D and pan-ERBB is synergistic in pancreatic ductal adenocarcinoma
Authors: Gulay Kevin Christian Montecillo. , Zhang Xinlian , Pantazopoulou Vasiliki , Patel Jay , Esparza Edgar , Pran Babu Deepa Sheik. , Ogawa Satoshi , Weitz Jonathan , Ng Isabella , Mose Evangeline S. , Pu Minya , Engle Dannielle D. , Lowy Andrew M. , Tiriac Hervé
Published: September 2024

Table S1. List of drugs used in this study.
Figure S4 from ESRRB inhibits the TGF-β signaling pathway to drive cell proliferation in cervical cancer
Authors: Li Qin-Shu , Zheng Peng-Sheng
Published: September 2024

Fig. S4 describes the prognostic analysis of SMAD7 expression; SAMD7 expression in xenograft; Dynamic regulation of SMAD7 by ESRRB.
Figure S1 from ESRRB inhibits the TGF-β signaling pathway to drive cell proliferation in cervical cancer
Authors: Li Qin-Shu , Zheng Peng-Sheng
Published: September 2024

Fig. S1 describes the pan-cancer analysis of ESRRB; cell line validation; tumor-free growth period of transplanted tumors in vivo; and apoptosis analysis.
Supplementary Materials and methods from Pre-existing immunity drives the response to neoadjuvant chemotherapy in esophageal adenocarcinoma
Authors: Arbore Giuseppina , Albarello Luca , Bucci Gabriele , Punta Marco , Cossu Andrea , Fanti Lorella , Maurizio Aurora , Di Mauro Francesco , Bilello Vito , Arrigoni Gianluigi , Bonfiglio Silvia , Biancolini Donatella , Puccetti Francesco , Elmore Ugo , Vago Luca , Cascinu Stefano , Tonon Giovanni , Rosati Riccardo , Casorati Giulia , Dellabona Paolo
Published: September 2024

Supplementary Materials and methods
Supplementary Table S1 from Supraphysiological Androgens Promote the Tumor Suppressive Activity of the Androgen Receptor Through cMYC Repression and Recruitment of the DREAM Complex
Authors: Nyquist Michael D. , Coleman Ilsa M. , Lucas Jared M. , Li Dapei , Hanratty Brian , Meade Hannah , Mostaghel Elahe A. , Plymate Stephen R. , Corey Eva , Haffner Michael C. , Nelson Peter S.
Published: September 2024

Table of genes comprising signatures.
Supplemental Figures 1-4 from Supraphysiological Androgens Promote the Tumor Suppressive Activity of the Androgen Receptor Through cMYC Repression and Recruitment of the DREAM Complex
Authors: Nyquist Michael D. , Coleman Ilsa M. , Lucas Jared M. , Li Dapei , Hanratty Brian , Meade Hannah , Mostaghel Elahe A. , Plymate Stephen R. , Corey Eva , Haffner Michael C. , Nelson Peter S.
Published: September 2024

Supplemental Figures 1-4
Table S9 from Crosstalk between myeloid and B cells shapes the distinct microenvironments of primary and secondary liver cancer
Authors: Chen Zhihang , Zhang Guopei , Ren Xiaoxue , Yao Zhijia , Zhou Qian , Ren Xuxin , Chen Shuling , Xu Lixia , Sun Kaiyu , Zeng Qianwen , Kuang Ming , Kuang Dong-Ming , Peng Sui
Published: September 2024

The RNA sequencing count data of 61 HCC and 62 CRLM tissues
Table S8 from Crosstalk between myeloid and B cells shapes the distinct microenvironments of primary and secondary liver cancer
Authors: Chen Zhihang , Zhang Guopei , Ren Xiaoxue , Yao Zhijia , Zhou Qian , Ren Xuxin , Chen Shuling , Xu Lixia , Sun Kaiyu , Zeng Qianwen , Kuang Ming , Kuang Dong-Ming , Peng Sui
Published: September 2024

Table S8
Table S4 from Crosstalk between myeloid and B cells shapes the distinct microenvironments of primary and secondary liver cancer
Authors: Chen Zhihang , Zhang Guopei , Ren Xiaoxue , Yao Zhijia , Zhou Qian , Ren Xuxin , Chen Shuling , Xu Lixia , Sun Kaiyu , Zeng Qianwen , Kuang Ming , Kuang Dong-Ming , Peng Sui
Published: September 2024

Table S4
Table S1 from Crosstalk between myeloid and B cells shapes the distinct microenvironments of primary and secondary liver cancer
Authors: Chen Zhihang , Zhang Guopei , Ren Xiaoxue , Yao Zhijia , Zhou Qian , Ren Xuxin , Chen Shuling , Xu Lixia , Sun Kaiyu , Zeng Qianwen , Kuang Ming , Kuang Dong-Ming , Peng Sui
Published: September 2024

Table S1
Figure S11 from Crosstalk between myeloid and B cells shapes the distinct microenvironments of primary and secondary liver cancer
Authors: Chen Zhihang , Zhang Guopei , Ren Xiaoxue , Yao Zhijia , Zhou Qian , Ren Xuxin , Chen Shuling , Xu Lixia , Sun Kaiyu , Zeng Qianwen , Kuang Ming , Kuang Dong-Ming , Peng Sui
Published: September 2024

Figure S11
Figure S10 from Crosstalk between myeloid and B cells shapes the distinct microenvironments of primary and secondary liver cancer
Authors: Chen Zhihang , Zhang Guopei , Ren Xiaoxue , Yao Zhijia , Zhou Qian , Ren Xuxin , Chen Shuling , Xu Lixia , Sun Kaiyu , Zeng Qianwen , Kuang Ming , Kuang Dong-Ming , Peng Sui
Published: September 2024

Figure S10
Supplementary Figure 4 from Galectin-1 mediates chronic STING activation in tumors to promote metastasis through MDSC recruitment
Authors: Nambiar Dhanya K. , Viswanathan Vignesh , Cao Hongbin , Zhang Weiruo , Guan Li , Chamoli Manish , Holmes Brittany , Kong Christina , Hildebrand Rachel , Koong Amanda Jeanette. , von Eyben Rie , Plevritis Sylvia , Li Lingyin , Giaccia Amato , Engleman Edgar , Le Quynh-Thu
Published: September 2024

A. Gating strategy for CD8+ T cells in the spleen of mice treated with either MOC2 WT/KO-Gal1 CM. B. Quantitation of PMN-MDSCs and T cells in the spleen of mice bearing KO-Gal1 tumors injected with either WT- or KO-Gal1 CM for 3 weeks. C. Graph showing the 48-plex mouse cytokine Luminex assay results performed on the 10x concentrated condition media from MOC2 WT/KO-Gal1 tumor cells. The media was collected in 3 independent experiments and run as a single batch. D. Gating strategy for CXCR2 staining on PMN-MDSCs isolated from the tumor and pre-metastatic lungs.
Supplementary Figure 3 from Galectin-1 mediates chronic STING activation in tumors to promote metastasis through MDSC recruitment
Authors: Nambiar Dhanya K. , Viswanathan Vignesh , Cao Hongbin , Zhang Weiruo , Guan Li , Chamoli Manish , Holmes Brittany , Kong Christina , Hildebrand Rachel , Koong Amanda Jeanette. , von Eyben Rie , Plevritis Sylvia , Li Lingyin , Giaccia Amato , Engleman Edgar , Le Quynh-Thu
Published: September 2024

A. Quantification of PMN-MDSCs (CD11b+Ly6Clo/intLy6G+) in the liver and kidneys of MOC2 WT- or KO-Gal1 tumor-bearing mice at matched tumor volumes in comparison with naïve mice. B. Gating strategy used to quantify Arginase (Arg1) and interleukin-10 (IL-10) expression on PMN-MDSCs isolated from the tumor or the lungs of naïve mice or mice with pre-metastatic niches (sub-gated on CD45+ live cells). C. Heat map showing differential gene expression from PMN-MDSCs isolated from tumor and lung tissues of MOC2 WT-Gal1 tumor-bearing mice compared with naïve neutrophils. D. STRING analysis showing two clusters of genes representing IL-17 and collagen synthesis pathways that are upregulated PMN-MDSCs isolated from pre-metastatic lung tissues. E. Reactome pathway enrichment analyses performed using RNA-SEQ data showing pathway represented by upregulated genes in PMN-MDSCs isolated from pre-metastatic lung tissues. F. Quantification of Trichrome staining intensity in mEERL WT- or KO-Gal1 tumor-bearing mice lungs, n=5/group. G. tSNE plot showing depletion of PMN-MDSCs in the blood following injection of anti-GR1 antibody in mice compared with isotype alone.
Table S2 from Intratumoral Microbiota Composition Regulates Chemoimmunotherapy Response in Esophageal Squamous Cell Carcinoma
Authors: Wu Hong , Leng Xuefeng , Liu Qianshi , Mao Tianqin , Jiang Tao , Liu Yiqiang , Li Feifei , Cao Chenhui , Fan Jun , Chen Liang , Chen Yaqi , Yao Quan , Lu Shun , Liang Renchuan , Hu Lanlin , Liu Mingxin , Wan Yejian , Li Zhaoshen , Peng Jun , Luo Qiyu , Zhou Hang , Yin Jun , Xu Ke , Lan Mei , Peng Xinhao , Lan Haitao , Li Gang , Han Yongtao , Zhang Xia , Xiao Zhi-Xiong Jim. , Lang Jinyi , Wang Guihua , Xu Chuan
Published: September 2024

Table S2 shows clinical characteristics of patients with esophageal squamous cell carcinoma (ESCC) who underwent NACI1 treatment.
Figure S7 from Intratumoral Microbiota Composition Regulates Chemoimmunotherapy Response in Esophageal Squamous Cell Carcinoma
Authors: Wu Hong , Leng Xuefeng , Liu Qianshi , Mao Tianqin , Jiang Tao , Liu Yiqiang , Li Feifei , Cao Chenhui , Fan Jun , Chen Liang , Chen Yaqi , Yao Quan , Lu Shun , Liang Renchuan , Hu Lanlin , Liu Mingxin , Wan Yejian , Li Zhaoshen , Peng Jun , Luo Qiyu , Zhou Hang , Yin Jun , Xu Ke , Lan Mei , Peng Xinhao , Lan Haitao , Li Gang , Han Yongtao , Zhang Xia , Xiao Zhi-Xiong Jim. , Lang Jinyi , Wang Guihua , Xu Chuan
Published: September 2024

Figure S7 shows fecal microbial transplantation (FMT) influenced the immune microenvironment of subcutaneous xenograft tumor tissues.
Figure S5 from Intratumoral Microbiota Composition Regulates Chemoimmunotherapy Response in Esophageal Squamous Cell Carcinoma
Authors: Wu Hong , Leng Xuefeng , Liu Qianshi , Mao Tianqin , Jiang Tao , Liu Yiqiang , Li Feifei , Cao Chenhui , Fan Jun , Chen Liang , Chen Yaqi , Yao Quan , Lu Shun , Liang Renchuan , Hu Lanlin , Liu Mingxin , Wan Yejian , Li Zhaoshen , Peng Jun , Luo Qiyu , Zhou Hang , Yin Jun , Xu Ke , Lan Mei , Peng Xinhao , Lan Haitao , Li Gang , Han Yongtao , Zhang Xia , Xiao Zhi-Xiong Jim. , Lang Jinyi , Wang Guihua , Xu Chuan
Published: September 2024

Figure S5 shows intra-tumoral Microbiota associated with activated immune cell infiltration.
Figure S2 from Intratumoral Microbiota Composition Regulates Chemoimmunotherapy Response in Esophageal Squamous Cell Carcinoma
Authors: Wu Hong , Leng Xuefeng , Liu Qianshi , Mao Tianqin , Jiang Tao , Liu Yiqiang , Li Feifei , Cao Chenhui , Fan Jun , Chen Liang , Chen Yaqi , Yao Quan , Lu Shun , Liang Renchuan , Hu Lanlin , Liu Mingxin , Wan Yejian , Li Zhaoshen , Peng Jun , Luo Qiyu , Zhou Hang , Yin Jun , Xu Ke , Lan Mei , Peng Xinhao , Lan Haitao , Li Gang , Han Yongtao , Zhang Xia , Xiao Zhi-Xiong Jim. , Lang Jinyi , Wang Guihua , Xu Chuan
Published: September 2024

Figure S2 shows intra-tumoral microbial diversity of patients with ESCC.
Supplementary Fig. S6 from Endocrine therapy synergizes with SMAC mimetics to potentiate antigen presentation and tumor regression in hormone receptor-positive breast cancer
Authors: Hermida-Prado Francisco , Xie Yingtian , Sherman Shira , Nagy Zsuzsanna , Russo Douglas , Akhshi Tara , Chu Zhengtao , Feit Avery , Campisi Marco , Chen Minyue , Nardone Agostina , Guarducci Cristina , Lim Klothilda , Font-Tello Alba , Lee Irene , García-Pedrero Juana , Canadas Israel , Agudo Judith , Huang Ying , Sella Tal , Jin Qingchun , Tayob Nabihah , Mittendorf Elizabeth A. , Tolaney Sara M. , Qiu Xintao , Long Henry , Symmans William F. , Lin Jia-Ren , Santagata Sandro , Bedrosian Isabelle , Yardley Denise A. , Mayer Ingrid A. , Richardson Edward T. , Oliveira Giacomo , Wu Catherine J. , Schuster Eugene F. , Dowsett Mitch , Welm Alana L. , Barbie David , Metzger Otto , Jeselsohn Rinath
Published: September 2024

Supplementary Fig. S6. Effect of hormone deprivation and NFKB pathway activation HR+ breast cancer cells.
Table S7 from LncRNA AGPG confers endocrine resistance in breast cancer by promoting E2F1 activity
Authors: Yu Shiyi , Wang Ying , Gong Xue , Fan Zhehao , Wang Zheng , Liang Zhengyan , Wu Rui , Cao Binjie , Wang Ning , Bi Caili , Lv Dan , Sun Haibo
Published: September 2024

Table S7
Figure S7 from LncRNA AGPG confers endocrine resistance in breast cancer by promoting E2F1 activity
Authors: Yu Shiyi , Wang Ying , Gong Xue , Fan Zhehao , Wang Zheng , Liang Zhengyan , Wu Rui , Cao Binjie , Wang Ning , Bi Caili , Lv Dan , Sun Haibo
Published: September 2024

Figure S7
Figure S6 from LncRNA AGPG confers endocrine resistance in breast cancer by promoting E2F1 activity
Authors: Yu Shiyi , Wang Ying , Gong Xue , Fan Zhehao , Wang Zheng , Liang Zhengyan , Wu Rui , Cao Binjie , Wang Ning , Bi Caili , Lv Dan , Sun Haibo
Published: September 2024

Figure S6
Figure S4 from LncRNA AGPG confers endocrine resistance in breast cancer by promoting E2F1 activity
Authors: Yu Shiyi , Wang Ying , Gong Xue , Fan Zhehao , Wang Zheng , Liang Zhengyan , Wu Rui , Cao Binjie , Wang Ning , Bi Caili , Lv Dan , Sun Haibo
Published: September 2024

Figure S4
Figure S1 from LncRNA AGPG confers endocrine resistance in breast cancer by promoting E2F1 activity
Authors: Yu Shiyi , Wang Ying , Gong Xue , Fan Zhehao , Wang Zheng , Liang Zhengyan , Wu Rui , Cao Binjie , Wang Ning , Bi Caili , Lv Dan , Sun Haibo
Published: September 2024

Figure S1
Supplementary Table S2 from Histone methyltransferase NSD2 activates PKCα to drive metabolic reprogramming and lenalidomide resistance in multiple myeloma
Authors: Chong Phyllis S.Y. , Chooi Jing-Yuan , Lim Julia S.L. , Leow Aaron C.Y. , Toh Sabrina Hui Min. , Azaman Irfan , Koh Mun Yee , Teoh Phaik Ju , Tan Tuan Zea , Chung Tae-Hoon , Chng Wee Joo
Published: September 2024

Supplementary Table S2
Supplementary Data from Histone methyltransferase NSD2 activates PKCα to drive metabolic reprogramming and lenalidomide resistance in multiple myeloma
Authors: Chong Phyllis S.Y. , Chooi Jing-Yuan , Lim Julia S.L. , Leow Aaron C.Y. , Toh Sabrina Hui Min. , Azaman Irfan , Koh Mun Yee , Teoh Phaik Ju , Tan Tuan Zea , Chung Tae-Hoon , Chng Wee Joo
Published: September 2024

Figure S1-9 and Supplementary Materials
Supplementary Figure S4 from Radiation therapy-induced neurocognitive impairment is driven by heightened apoptotic priming in early life and prevented by blocking BAX
Authors: Singh Rumani , Yu Stacey , Osman Marwa , Inde Zintis , Fraser Cameron , Cleveland Abigail H. , Almanzar Nicole , Lim Chuan Bian , Joshi Gaurav N. , Spetz Johan , Qin Xingping , Toprani Sneh M. , Nagel Zachary , Hocking Matthew C. , Cormack Robert A. , Yock Torunn I. , Miller Jeffrey W. , Yuan Zhi-Min , Gershon Timothy , Sarosiek Kristopher A.
Published: September 2024

Supplementary Figure S4
Supplementary Table S4 from Single-cell characterization of pulmonary nodules implicates suppression of immunosurveillance across early stages of lung adenocarcinoma
Authors: Yanagawa Jane , Tran Linh M. , Salehi-Rad Ramin , Lim Raymond J. , Dumitras Camelia , Fung Eileen , Wallace William D. , Prosper Ashley E. , Fishbein Gregory , Shea Conor , Hong Rui , Kahangi Bitta , Deng John J. , Gower Adam C. , Liu Bin , Campbell Joshua D. , Mazzilli Sarah A. , Beane Jennifer E. , Kadara Humam , Lenburg Marc E. , Spira Avrum E. , Aberle Denise R. , Krysan Kostyantyn , Dubinett Steven M.
Published: September 2024

DEGs between subsolid nodule and nLung C20 NKT cells
Supplementary Figures from Single-cell characterization of pulmonary nodules implicates suppression of immunosurveillance across early stages of lung adenocarcinoma
Authors: Yanagawa Jane , Tran Linh M. , Salehi-Rad Ramin , Lim Raymond J. , Dumitras Camelia , Fung Eileen , Wallace William D. , Prosper Ashley E. , Fishbein Gregory , Shea Conor , Hong Rui , Kahangi Bitta , Deng John J. , Gower Adam C. , Liu Bin , Campbell Joshua D. , Mazzilli Sarah A. , Beane Jennifer E. , Kadara Humam , Lenburg Marc E. , Spira Avrum E. , Aberle Denise R. , Krysan Kostyantyn , Dubinett Steven M.
Published: September 2024

Figure S1 - S8, Table S1-S2
Supplementary Table 2 from Spatial profiling of circular RNAs in cancer reveals high expression in muscle and stromal cells
Authors: García-Rodríguez Juan L. , Korsgaard Ulrik , Ahmadov Ulvi , Jarlstad Olesen Morten T. , Dietrich Kim-Gwendolyn , Hansen Emma B. , Vissing Stine M. , Ulhøi Benedicte P. , Dyrskjøt Lars , Sørensen Karina D. , Kjems Jørgen , Hager Henrik , Kristensen Lasse S.
Published: September 2024

List of reference genes, tissue markers genes and top circular RNAs for which nanostring nCounter probes were designed.
Supplementary Fig. 6 from Spatial profiling of circular RNAs in cancer reveals high expression in muscle and stromal cells
Authors: García-Rodríguez Juan L. , Korsgaard Ulrik , Ahmadov Ulvi , Jarlstad Olesen Morten T. , Dietrich Kim-Gwendolyn , Hansen Emma B. , Vissing Stine M. , Ulhøi Benedicte P. , Dyrskjøt Lars , Sørensen Karina D. , Kjems Jørgen , Hager Henrik , Kristensen Lasse S.
Published: September 2024

Expression levels of MKI67. Measurement of levels of MKI67 by RT-qPCR normalized to MRPL19.
Supplementary Fig. 3 from Spatial profiling of circular RNAs in cancer reveals high expression in muscle and stromal cells
Authors: García-Rodríguez Juan L. , Korsgaard Ulrik , Ahmadov Ulvi , Jarlstad Olesen Morten T. , Dietrich Kim-Gwendolyn , Hansen Emma B. , Vissing Stine M. , Ulhøi Benedicte P. , Dyrskjøt Lars , Sørensen Karina D. , Kjems Jørgen , Hager Henrik , Kristensen Lasse S.
Published: September 2024

Heatmap and unsupervised hierarchical clustering of normalized nanostring nCounter data from cancer cells, tumor stroma and normal epithelium. A clearer clustering of these sample groups can be observed when the muscularis propria samples are not included in the analysis.
Figure S8 from Targeting the immunoglobulin IGSF9 enhances anti-tumor T cell activity and sensitivity to anti-PD-1 immunotherapy
Authors: Liu Yifan , Wang Hongying , Zhao Xinyu , Zhang Jiashen , Zhao Zhiling , Lian Xia , Zhang Juan , Kong Feng , Hu Tao , Wang Ting , Li Xiaohua , Wang Lei , Wang Dapeng , Li Chunling , Luan Huiwen , Liu Xiaoli , Wang Chunyan , Jiang Yun , Li Xiaomin , Li Fangmin , Ji Shuhao , Wang Yaopeng , Li Zunling
Published: September 2024

Anti-IGSF9 regained the activation of T cells.
Supplementary Data from The ratio of key metabolic transcripts is a predictive biomarker of breast cancer metastasis to the lung
Authors: Mathur Deepti , Liao Chen , Lin Wendy , La Ferlita Alessandro , Alaimo Salvatore , Taylor Samuel , Zhong Yi , Iacobuzio-Donahue Christine , Ferro Alfredo , Xavier Joao B.
Published: September 2024

Supplementary figures and figure legends
Supplementary Data from Development of a rare earth nanoprobe enables in vivo real-time detection of sentinel lymph node metastasis of breast cancer using NIR-IIb imaging
Authors: Zhu Yuan-Yuan , Song Liang , Zhang Yong-Qu , Liu Wan-Ling , Chen Wei-Ling , Gao Wen-Liang , Zhang Li-Xin , Wang Jia-Zheng , Ming Zi-He , Zhang Yun , Zhang Guo-Jun
Published: September 2024

All Supplementary Data
Figure S3 from Breast cancer-secreted factors promote lung metastasis by signaling systemically to induce a fibrotic pre-metastatic niche
Authors: Cohen Noam , Mundhe Dhanashree , Deasy Sarah K. , Adler Omer , Ershaid Nour , Shami Tamar , Levi-Galibov Oshrat , Wassermann Rina , Scherz-Shouval Ruth , Erez Neta
Published: September 2024

Supplementary data to Figure 6
Supplementary Data from The IGF2BP3-COPS7B axis facilitates mRNA translation to drive colorectal cancer progression
Authors: Tang Jing , Wang Shuoshuo , Weng Mingjiao , Guo Qingyu , Ren Lili , He Yan , Cui Zihan , Cong Mingqi , Qin Minglu , Yu Jia , Su Rui , Li Xiaobo
Published: September 2024

Supplementary Figures
Supp. Figure 2 from Parkin deficiency suppresses antigen presentation to promote tumor immune evasion and immunotherapy resistance
Authors: Perales-Linares Renzo , Leli Nektaria Maria , Mohei Hesham , Beghi Silvia , Rivera Osvaldo D. , Kostopoulos Nektarios , Giglio Andrea , George Subin S. , Uribe-Herranz Mireia , Costabile Francesca , Pierini Stefano , Pustylnikov Sergei , Skoufos Giorgos , Barash Yoseph , Hatzigeorgiou Artemis G. , Koumenis Constantinos , Maity Amit , Lotze Michael T. , Facciabene Andrea
Published: September 2024

Figure S2
Supp. Figure 1 from Parkin deficiency suppresses antigen presentation to promote tumor immune evasion and immunotherapy resistance
Authors: Perales-Linares Renzo , Leli Nektaria Maria , Mohei Hesham , Beghi Silvia , Rivera Osvaldo D. , Kostopoulos Nektarios , Giglio Andrea , George Subin S. , Uribe-Herranz Mireia , Costabile Francesca , Pierini Stefano , Pustylnikov Sergei , Skoufos Giorgos , Barash Yoseph , Hatzigeorgiou Artemis G. , Koumenis Constantinos , Maity Amit , Lotze Michael T. , Facciabene Andrea
Published: September 2024

Figure S1
Tables S7-S9 from Integrative genomic analyses identify lncRNA regulatory networks across pediatric leukemias and solid tumors
Authors: Modi Apexa , Lopez Gonzalo , Conkrite Karina L. , Su Chun , Leung Tsz Ching , Ramanan Sathvik , Manduchi Elisabetta , Johnson Matthew E. , Cheung Daphne , Gadd Samantha , Zhang Jinghui , Smith Malcolm A. , Guidry Auvil Jaime M. , Meshinchi Soheil , Perlman Elizabeth J. , Hunger Stephen P. , Maris John M. , Wells Andrew D. , Grant Struan F.A. , Diskin Sharon J.
Published: September 2024

Table S7: Number of TARGET samples with WGS and SCNA events per cancer identified by GISTIC, Table S8: Differential expression of genes in samples with and without SCNA, Table S9: Number of samples with SVs in lncRNAs
Tables S13-S14 from Integrative genomic analyses identify lncRNA regulatory networks across pediatric leukemias and solid tumors
Authors: Modi Apexa , Lopez Gonzalo , Conkrite Karina L. , Su Chun , Leung Tsz Ching , Ramanan Sathvik , Manduchi Elisabetta , Johnson Matthew E. , Cheung Daphne , Gadd Samantha , Zhang Jinghui , Smith Malcolm A. , Guidry Auvil Jaime M. , Meshinchi Soheil , Perlman Elizabeth J. , Hunger Stephen P. , Maris John M. , Wells Andrew D. , Grant Struan F.A. , Diskin Sharon J.
Published: September 2024

Table S13: lncRNAs associated with CRC of NBL, Table S14: Differentially expressed lncRNAs between major subtypes in NBL
Figure S6 from Integrative genomic analyses identify lncRNA regulatory networks across pediatric leukemias and solid tumors
Authors: Modi Apexa , Lopez Gonzalo , Conkrite Karina L. , Su Chun , Leung Tsz Ching , Ramanan Sathvik , Manduchi Elisabetta , Johnson Matthew E. , Cheung Daphne , Gadd Samantha , Zhang Jinghui , Smith Malcolm A. , Guidry Auvil Jaime M. , Meshinchi Soheil , Perlman Elizabeth J. , Hunger Stephen P. , Maris John M. , Wells Andrew D. , Grant Struan F.A. , Diskin Sharon J.
Published: September 2024

Figure S6: Defining mesenchymal vs adrenergic lncRNAs in two NBL cohorts
Figure S2 from Integrative genomic analyses identify lncRNA regulatory networks across pediatric leukemias and solid tumors
Authors: Modi Apexa , Lopez Gonzalo , Conkrite Karina L. , Su Chun , Leung Tsz Ching , Ramanan Sathvik , Manduchi Elisabetta , Johnson Matthew E. , Cheung Daphne , Gadd Samantha , Zhang Jinghui , Smith Malcolm A. , Guidry Auvil Jaime M. , Meshinchi Soheil , Perlman Elizabeth J. , Hunger Stephen P. , Maris John M. , Wells Andrew D. , Grant Struan F.A. , Diskin Sharon J.
Published: September 2024

Figure S2: lncRNA expression varies across pediatric cancers
Figure S1 from Integrative genomic analyses identify lncRNA regulatory networks across pediatric leukemias and solid tumors
Authors: Modi Apexa , Lopez Gonzalo , Conkrite Karina L. , Su Chun , Leung Tsz Ching , Ramanan Sathvik , Manduchi Elisabetta , Johnson Matthew E. , Cheung Daphne , Gadd Samantha , Zhang Jinghui , Smith Malcolm A. , Guidry Auvil Jaime M. , Meshinchi Soheil , Perlman Elizabeth J. , Hunger Stephen P. , Maris John M. , Wells Andrew D. , Grant Struan F.A. , Diskin Sharon J.
Published: September 2024

Figure S1: Workflow for RNA-seq gene mapping and quantification
Data from Germline cancer gene expression quantitative trait loci are associated with local and global tumor mutations
Authors: Liu Yuxi , Gusev Alexander , Kraft Peter
Published: September 2024

Abstract
Somatic mutations drive cancer development and are relevant to patient responses to treatment. Emerging evidence shows that variations in the somatic genome can be influenced by the germline genetic background. However, the mechanisms underlying these germline-somatic associations remain largely obscure. We hypothesized that germline variants can influence somatic mutations in a nearby cancer gene (“local impact”) or a set of recurrently mutated cancer genes across the genome (“global impact”) through their regulatory effect on gene expression. To test this hypothesis, tumor targeted sequencing data from 12,413 patients across 11 cancer types in the Dana-Farber Profile cohort were integrated with germline cancer gene expression quantitative trait loci (eQTL) from the Genotype-Tissue Expression Project. Variants that upregulate ATM expression were associated with a decreased risk of somatic ATM mutations across 8 cancer types. GLI2, WRN, and CBFB eQTL were associated with global tumor mutational burden of cancer genes in ovarian cancer, glioma, and esophagogastric carcinoma, respectively. An EPHA5 eQTL was associated with mutations in cancer genes specific to colorectal cancer, and eQTL related to expression of APC, WRN, GLI1, FANCA, and TP53 were associated with mutations in genes specific to endometrial cancer. These findings provide evidence that germline-somatic associations are mediated through expression of specific cancer genes, opening new avenues for research on the underlying biological processes.
Data from Polyunsaturated fatty acid-bound alpha-fetoprotein promotes immune suppression by altering human dendritic cell metabolism
Authors: Munson Paul V. , Adamik Juraj , Hartmann Felix J. , Favaro Patricia M. B. , Ho Daniel , Bendall Sean C. , Combes Alexis J. , Krummel Matthew F. , Zhang Karen , Kelley Robin K. , Butterfield Lisa H.
Published: September 2024

Abstract
Alpha-fetoprotein (AFP) is expressed by stem-like and poor outcome hepatocellular cancer tumors and is a clinical tumor biomarker. AFP has been demonstrated to inhibit dendritic cell differentiation and maturation and to block oxidative phosphorylation. To identify the critical metabolic pathways leading to human dendritic cell functional suppression, here we utilized two recently described single cell profiling methods, scMEP (single-cell metabolic profiling) and SCENITH (single-cell energetic metabolism by profiling translation inhibition). Glycolytic capacity and glucose dependence of dendritic cells was significantly increased by tumor-derived, but not normal cord blood-derived, AFP, leading to increased glucose uptake and lactate secretion. Key molecules in the electron transport chain in particular were regulated by tumor-derived AFP. These metabolic changes occurred at mRNA and protein levels, with negative impact on dendritic cell stimulatory capacity. Tumor-derived AFP bound significantly more polyunsaturated fatty acids than cord blood-derived AFP. Polyunsaturated fatty acids bound to AFP increased metabolic skewing and promoted dendritic cell functional suppression. Polyunsaturated fatty acids inhibited dendritic cell differentiation in vitro, and ω-6 polyunsaturated fatty acids conferred potent immunoregulation when bound to tumor-derived AFP. Together, these findings provide mechanistic insights into how AFP antagonizes the innate immune response to limit anti-tumor immunity.
Data from NAT10 drives cisplatin chemoresistance by enhancing ac4C-associated DNA repair in bladder cancer
Authors: Xie Ruihui , Cheng Liang , Huang Ming , Huang Lin , Chen Ziyue , Zhang Qiang , Li Hong , Lu Junlin , Wang Hongjin , Zhou Qianghua , Huang Jian , Chen Xu , Lin Tianxin
Published: September 2024

Abstract
Epitranscriptomic RNA modifications constitute a critical gene regulatory component that can affect cancer progression. Among these, the RNA N4-acetylcytidine (ac4C) modification, which is mediated by the ac4C writer N-acetyltransferase 10 (NAT10), regulates the stabilization of mRNA. Here, we identified that the ac4C modification is induced upon cisplatin treatment and correlates with chemoresistance in bladder cancer (BCa). Both in vitro and in vivo, NAT10 promoted cisplatin chemoresistance in BCa cells by enhancing DNA damage repair. Mechanistically, NAT10 bound and stabilized AHNAK mRNA by protecting it from exonucleases, and AHNAK-mediated DNA damage repair was required for NAT10-induced cisplatin resistance. Clinically, NAT10 overexpression was associated with chemoresistance, recurrence, and worse clinical outcome in BCa patients. Cisplatin-induced NFκB signaling activation was required for the upregulation of NAT10 expression, and NFκB p65 directly bound to the NAT10 promoter to activate transcription. Moreover, pharmacological inhibition of NAT10 with Remodelin sensitized BCa organoids and mouse xenografts to cisplatin. Overall, the present study uncovered a mechanism of NAT10-mediated mRNA stabilization in BCa, laying the foundation for NAT10 as a therapeutic target to overcome cisplatin resistance in BCa.
Data from Nucleophosmin plays a role in repairing DNA damage and is a target for cancer treatment
Authors: Sekhar Konjeti R. , Freeman Michael L.
Published: September 2024

Abstract
Nucleophosmin (NPM1) is frequently mutated in acute myeloid leukemia, and NPM1 expression is elevated in several cancer types. NPM1 is a multifunctional oligomeric protein involved in numerous cellular functions that include participating in liquid-liquid phase separation, ribosome biogenesis, chaperoning of histones, and modulation of transcription. In this review, we discuss the underappreciated role of NPM1 in DNA damage repair, specifically Polη-mediated translesion synthesis, base excision, and homologous recombination and highlight the therapeutic potential of NPM1 targeting in cancer treatment.
Data from Comprehensive DNA methylation analysis indicates that pancreatic intraepithelial neoplasia lesions are acinar-derived and epigenetically primed for carcinogenesis
Authors: Lo Emily K. W. , Mears Brian M. , Maurer H. Carlo , Idrizi Adrian , Hansen Kasper D. , Thompson Elizabeth D. , Hruban Ralph H. , Olive Kenneth P. , Feinberg Andrew P.
Published: September 2024

Abstract
Pancreatic ductal adenocarcinoma (PDAC) is believed to arise from the accumulation of a series of somatic mutations and is also frequently associated with pancreatic intraepithelial neoplasia (PanIN) lesions. However, there is still debate as to whether the cell-type-of-origin of PanINs and PDACs in humans is acinar or ductal. As cell type identity is maintained epigenetically, DNA methylation changes during pancreatic neoplasia can provide a compelling perspective to examine this question. Here, we performed laser-capture microdissection on surgically resected specimens from 18 patients to isolate, with high purity, DNA for whole-genome bisulfite sequencing from four relevant cell types: acini, non-neoplastic ducts, PanIN lesions, and PDAC lesions. Differentially methylated regions (DMRs) were identified using two complementary analytical approaches: bsseq, which identifies any DMRs but is particularly useful for large block-like DMRs; and informME which profiles the potential energy landscape across the genome and is particularly useful for identifying differential methylation entropy. Both global methylation profiles and block DMRs clearly implicated an acinar origin for PanINs. At the gene level, PanIN lesions exhibited an intermediate acinar-ductal phenotype resembling acinar-to-ductal metaplasia. In 97.6% of PanIN-specific DMRs, PanIN lesions had an intermediate methylation level between normal and PDAC, which suggests from an information theory perspective that PanIN lesions are epigenetically primed to progress to PDAC. Thus, epigenomic analysis complements histopathology to define molecular progression toward PDAC. The shared epigenetic lineage between PanIN and PDAC lesions could provide an opportunity for prevention by targeting aberrantly methylated progression-related genes.
Data from Angiopoietin-2-dependent spatial vascular destabilization promotes T-cell exclusion and limits immunotherapy in melanoma
Authors: Park Ha-Ram , Shiva Anahita , Cummings Portia , Kim Seoyeon , Kim Sungsoo , Lee Eunhyeong , Leong Alessandra , Chowdhury Subrata , Shawber Carrie , Carvajal Richard , Thurston Gavin , An Joon Yong , Lund Amanda W. , Yang Hee Won , Kim Minah
Published: September 2024

Abstract
T cell position in the tumor microenvironment determines the probability of target encounter and tumor killing. CD8+ T cell exclusion from the tumor parenchyma is associated with poor response to immunotherapy, and yet the biology that underpins this distinct pattern remains unclear. Here we show that the vascular destabilizing factor angiopoietin-2 (ANGPT2) causes compromised vascular integrity in the tumor periphery, leading to impaired T cell infiltration to the tumor core. The spatial regulation of ANGPT2 in whole tumor cross-sections was analyzed in conjunction with T cell distribution, vascular integrity, and response to immunotherapy in syngeneic murine melanoma models. T cell exclusion was associated with ANGPT2 upregulation and elevated vascular leakage at the periphery of human and murine melanomas. Both pharmacological and genetic blockade of ANGPT2 promoted CD8+ T cell infiltration into the tumor core, exerting antitumor effects. Importantly, the reversal of T cell exclusion following ANGPT2 blockade not only enhanced response to anti-PD-1 immune checkpoint blockade therapy in immunogenic, therapy responsive mouse melanomas, but it also rendered non-responsive tumors susceptible to immunotherapy. Therapeutic response after ANGPT2 blockade, driven by improved CD8+ T cell infiltration to the tumor core, coincided with spatial TIE2 signaling activation and increased vascular integrity at the tumor periphery where endothelial expression of adhesion molecules was reduced. These data highlight ANGPT2/TIE2 signaling as a key mediator of T cell exclusion and a promising target to potentiate immune checkpoint blockade efficacy in melanoma.
Data from Attenuation of sialylation augments antitumor immunity and improves response to immunotherapy in ovarian cancer
Authors: Cao Kankan , Zhang Guodong , Yang Moran , Wang Yiying , He Mengdi , Zhang Chen , Huang Yan , Lu Jiaqi , Liu Haiou
Published: September 2024

Abstract
Aberrant sialylation functions as an important modulator of all steps of malignant transformation. Therefore, targeting sialylation regulators, such as sialyltransferases and neuraminidases, is a potential strategy for treating cancer. Here, we found that elevated α2,3-sialyltransferase III (St3gal3) was associated with dismal prognosis in high-grade serous ovarian carcinoma (HGSC). St3gal3 knockdown antagonized subcutaneous tumor growth in immunocompetent, but not immunodeficient mice, with enhanced accumulation of functional CD8+ T cells and anti-tumor immune gene signatures. St3gal3 knockdown inhibited intraperitoneal tumor growth and repolarized tumor-associated macrophages from a pro-tumorigenic M2-like to a tumor-suppressive M1-like phenotype. In vitro, St3gal3 knockdown tumor cells guided bone marrow-derived macrophages (BMDM) toward the M1-like phenotype under both direct contact and distant transwell co-culture conditions. Depletion of macrophages rescued the suppressed tumor growth induced by St3gal3 knockdown and completely suppressed infiltration of functional CD8+ T cells that rely on macrophage-derived CXCL10. St3gal3 engendered an immunosuppressive HGSC microenvironment characterized by an abundance of pro-tumorigenic macrophages and reduced cytotoxic T cell infiltration. In vivo, St3gal3 knockdown improved effectiveness of dual immune checkpoint blockade (ICB) with αPD-1 and αCTLA-4 antibodies. Preclinical inhibition of sialylation with ambroxol resulted in decreased tumor growth and prolonged the survival of tumor-bearing mice, which was enhanced by the addition of dual ICB. These findings indicate that altered sialylation induced by St3gal3 upregulation promotes a tumor suppressive microenvironment in HGSC and targeting α2,3-sialylation may reprogram the immunosuppressive tumor microenvironment and improve the efficacy of immunotherapy.
Data from Retinol saturase mediates retinoid metabolism to impair a ferroptosis defense system in cancer cells
Authors: Bi Guoshu , Liang Jiaqi , Shan Guangyao , Bian Yunyi , Chen Zhencong , Huang Yiwei , Lu Tao , Li Ming , Besskaya Valeria , Zhao Mengnan , Fan Hong , Wang Qun , Gan Boyi , Zhan Cheng
Published: September 2024

Abstract
Ferroptosis is an iron-dependent form of regulated cell death induced by the lethal overload of lipid peroxides in cellular membranes. In recent years, modulating ferroptosis has gained attention as a potential therapeutic approach for tumor suppression. In the present study, retinol saturase (RETSAT) was identified as a significant ferroptosis mediator using a publicly accessible CRISPR/Cas9 screening dataset. RETSAT depletion protected tumor cells from lipid peroxidation and subsequent cell death triggered by various ferroptosis inducers. Furthermore, exogenous supplementation with retinoids, including retinol (the substrate of RETSAT) and its derivatives retinal and retinoic acid, also suppressed ferroptosis, whereas the product of RETSAT, 13, 14-dihydroretinol, failed to do so. As effective radical-trapping antioxidant, retinoids protected the lipid membrane from autoxidation and subsequent fragmentation, thus terminating the cascade of ferroptosis. Pseudotargeted lipidomic analysis identified an association between retinoid regulation of ferroptosis and lipid metabolism. Retinoic acid, but not 13, 14-dihydroretinoic acid, interacted with its nuclear receptor and activated transcription of SCD, which introduces the first double bond into saturated fatty acid and thus catalyzes the generation of monounsaturated fatty acid, a known ferroptosis suppressor. Therefore, RETSAT promotes ferroptosis by transforming retinol to 13, 14-dihydroretinol, thereby turning a strong anti-ferroptosis regulator into a relatively weak one.
Data from The HDAC2-SP1 axis orchestrates pro-tumor macrophage polarization
Authors: Zheng Xiang , Sarode Poonam , Weigert Andreas , Turkowski Kati , Chelladurai Prakash , Günther Stefan , Kuenne Carsten , Winter Hauke , Stenzinger Albrecht , Reu Simone , Grimminger Friedrich , Stiewe Thorsten , Seeger Werner , Pullamsetti Soni Savai. , Savai Rajkumar
Published: September 2024

Abstract
Tumor-associated macrophages (TAMs), including anti-tumor M1-like TAMs and pro-tumor M2-like TAMs, are transcriptionally dynamic innate immune cells with diverse roles in lung cancer development. Epigenetic regulators are key in controlling macrophage fate in the heterogeneous tumor microenvironment. Here, we demonstrate that the spatial proximity of HDAC2–overexpressing M2-like TAMs to tumor cells significantly correlates with poor overall survival of lung cancer patients. Suppression of HDAC2 in TAMs altered macrophage phenotype, migration, and signaling pathways related to interleukins, chemokines, cytokines, and T cell activation. In co-culture systems of TAMs and cancer cells, suppressing HDAC2 in TAMs resulted in reduced proliferation and migration, increased apoptosis of cancer cell lines and primary lung cancer cells, and attenuated endothelial cell tube formation. HDAC2 regulated the M2-like TAM phenotype via acetylation of histone H3 and transcription factor SP1. Myeloid cell–specific deletion of Hdac2 and pharmacological inhibition of class I HDACs in four different murine lung cancer models induced the switch from M2-like to M1-like TAMs, altered infiltration of CD4+ and CD8+ T cells, and reduced tumor growth and angiogenesis. TAM-specific HDAC2 expression may provide a biomarker for lung cancer stratification and a target for developing improved therapeutic approaches.
Data from Metformin reprograms tryptophan metabolism to stimulate CD8+ T cell function in colorectal cancer
Authors: Huang Xiaowen , Sun Tiantian , Wang Jilin , Hong Xialu , Chen Huimin , Yan Tingting , Zhou Chengbei , Sun Danfeng , Yang Chen , Yu TaChung , Su Wenyu , Du Wan , Xiong Hua
Published: September 2024

Abstract
Colorectal carcinogenesis coincides with immune cell dysfunction. Metformin has been reported to play a role in stimulating anti-tumor immunity, suggesting it could be used to overcome immunosuppression in colorectal cancer (CRC). Herein, using single-cell RNA sequencing, we showed that metformin remodels the immune landscape of CRC. In particular, metformin treatment expanded the proportion of CD8+ T cells and potentiated their function. Analysis of the metabolic activities of cells in the CRC tumor microenvironment (TME) at a single-cell resolution demonstrated that metformin reprogrammed tryptophan metabolism, which was reduced in CRC cells and increased in CD8+ T cells. Untreated CRC cells outcompeted CD8+ T cells for tryptophan, leading to impaired CD8+ T cell function. Metformin in turn reduced tryptophan uptake by CRC cells, thereby restoring tryptophan availability for CD8+ T cells and increasing their cytotoxicity. Metformin inhibited tryptophan uptake in CRC cells by downregulating MYC, which led to a reduction in the tryptophan transporter SLC7A5. This work highlights metformin as an essential regulator of T-cell antitumor immunity by reprogramming tryptophan metabolism, suggesting it could be a potential immunotherapeutic strategy for treating CRC.
Data from Ccr2+ monocyte-derived macrophages influence trajectories of acquired therapy resistance in Braf-mutant melanoma
Authors: Kim Dahihm , An Luye , Moon Jiwon , Maymi Viviana I. , McGurk Alexander I. , Rudd Brian D. , Fowell Deborah , White Andrew C.
Published: September 2024

Abstract
Therapies targeting oncogene addiction have had a tremendous impact on tumor growth and patient outcome, but drug resistance continues to be problematic. One approach to deal with the challenge of resistance entails extending anti-cancer treatments beyond targeting cancer cells by additionally altering the tumor microenvironment. Understanding how the tumor microenvironment contributes to the evolution of diverse resistance pathways could aid in the design of sequential treatments that can elicit and take advantage of a predictable resistance trajectory. Tumor associated macrophages often support neoplastic growth and are frequently the most abundant immune cell found in tumors. Here, we used clinically relevant in vivo Braf-mutant melanoma models with fluorescent markers to track the stage-specific changes in macrophages under targeted therapy with Braf/Mek inhibitors and assessed the dynamic evolution of the macrophage population generated by therapy pressure-induced stress. During the onset of a drug-tolerant persister state, Ccr2+ monocyte-derived macrophage infiltration rose, suggesting that macrophage influx at this point could facilitate the onset of stable drug resistance. Comparison of melanomas that develop in a Ccr2-proficient or deficient microenvironment demonstrated that lack of melanoma infiltrating Ccr2+ macrophages delayed onset of resistance and shifted melanoma cell evolution towards unstable resistance. Unstable resistance was characterized by sensitivity to targeted therapy when factors from the microenvironment were lost. Importantly, this phenotype was reversed by co-culturing melanoma cells with Ccr2+ macrophages. Overall, this study demonstrates that the development of resistance may be directed by altering the tumor microenvironment to improve treatment timing and the probability of relapse.