156. Kroemer G, Galassi C, Zitvogel L, Galluzzi L. Immunogenic cell stress and death. *Nat Immunol* (2022) 23(4):487–500. doi: 10.1038/s41590-022-01132-2

157. Zaretsky JM, Garcia-Diaz A, Shin DS, Escuin-Ordinas H, Hugo W, Hu-Lieskovan S, et al. Mutations associated with acquired resistance to PD-1 blockade in melanoma. *N Engl J Med* (2016) 375(9):819–29. doi: 10.1056/NEJMoa1604958

158. Anagnostou V, Smith KN, Forde PM, Niknafs N, Bhattacharya R, White J, et al. Evolution of neoantigen landscape during immune checkpoint blockade in non-small cell lung cancer. *Cancer Discov* (2017) 7(3):264–76. doi: 10.1158/2159-8290.CD-16-0828

159. Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. *Annu Rev Immunol* (2004) 22:329–60. doi: 10.1146/annurev.immunol.22.012703.104803

160. Chan JM, Quintanal-Villalonga À, Gao VR, Xie Y, Allaj V, Chaudhary O, et al. Signatures of plasticity, metastasis, and immunosuppression in an atlas of human small cell lung cancer. *Cancer Cell* (2021) 39(11):1479–96. doi: 10.1016/j.ccell.2021.09.008

161. Ortiz-Cuaran S, Swalduz A, Foy JP, Marteau S, Morel AP, Fauvet F, et al. Epithelial-to-mesenchymal transition promotes immune escape by inducing CD70 in

non-small cell lung cancer. *Eur J Cancer* (2022) 169:106–22. doi: 10.1016/j.ejca.2022.03.038

162. Taki M, Abiko K, Ukita M, Murakami R, Yamanoi K, Yamaguchi K, et al. Tumor immune microenvironment during epithelial–mesenchymal transition. *Clin Cancer Res* (2021) 27(17):4669–79. doi: 10.1158/1078-0432.CCR-20-4459

163. Faget J, Groeneveld S, Boivin G, Sankar M, Zangger N, Garcia M, et al. Neutrophils and snail orchestrate the establishment of a pro-tumor microenvironment in lung cancer. *Cell Rep* (2017) 21(11):3190–204. doi: 10.1016/j.celrep.2017.11.052

164. Huang JQ, Wei FK, Xu XL, Ye SX, Song JW, Ding PK, et al. SOX9 drives the epithelial-mesenchymal transition in non-small-cell lung cancer through the wnt/β-catenin pathway. *J Transl Med* (2019) 17(1):143. doi: 10.1186/s12967-019-1895-2

165. Liu L, Zhu H, Liao Y, Wu W, Liu L, Liu L, et al. Inhibition of wnt/β-catenin pathway reverses multi-drug resistance and EMT in Oct4+/Nanog+ NSCLC cells. *BioMed Pharmacother* (2020) 127:110225. doi: 10.1016/j.biopha.2020.110225
156. Kroemer G, Galassi C, Zitvogel L, Galluzzi L. Immunogenic cell stress and death. *Nat Immunol* (2022) 23(4):487–500. doi: 10.1038/s41590-022-01132-2

157. Zaretsky JM, Garcia-Diaz A, Shin DS, Escuin-Ordinas H, Hugo W, Hu-Lieskovan S, et al. Mutations associated with acquired resistance to PD-1 blockade in melanoma. *N Engl J Med* (2016) 375(9):819–29. doi: 10.1056/NEJMoa1604958

158. Anagnostou V, Smith KN, Forde PM, Niknafs N, Bhattacharya R, White J, et al. Evolution of neoantigen landscape during immune checkpoint blockade in non-small cell lung cancer. *Cancer Discov* (2017) 7(3):264–76. doi: 10.1158/2159-8290.CD-16-0828

159. Dunn GP, Old LJ, Schreiber RD. The three Es of cancer immunoediting. *Annu Rev Immunol* (2004) 22:329–60. doi: 10.1146/annurev.immunol.22.012703.104803

160. Chan JM, Quintanal-Villalonga À, Gao VR, Xie Y, Allaj V, Chaudhary O, et al. Signatures of plasticity, metastasis, and immunosuppression in an atlas of human small cell lung cancer. *Cancer Cell* (2021) 39(11):1479–96. doi: 10.1016/j.ccell.2021.09.008

161. Ortiz-Cuaran S, Swalduz A, Foy JP, Marteau S, Morel AP, Fauvet F, et al. Epithelial-to-mesenchymal transition promotes immune escape by inducing CD70 in

non-small cell lung cancer. *Eur J Cancer* (2022) 169:106–22. doi: 10.1016/j.ejca.2022.03.038

162. Taki M, Abiko K, Ukita M, Murakami R, Yamanoi K, Yamaguchi K, et al. Tumor immune microenvironment during epithelial–mesenchymal transition. *Clin Cancer Res* (2021) 27(17):4669–79. doi: 10.1158/1078-0432.CCR-20-4459

163. Faget J, Groeneveld S, Boivin G, Sankar M, Zangger N, Garcia M, et al. Neutrophils and snail orchestrate the establishment of a pro-tumor microenvironment in lung cancer. *Cell Rep* (2017) 21(11):3190–204. doi: 10.1016/j.celrep.2017.11.052

164. Huang JQ, Wei FK, Xu XL, Ye SX, Song JW, Ding PK, et al. SOX9 drives the epithelial-mesenchymal transition in non-small-cell lung cancer through the wnt/β-catenin pathway. *J Transl Med* (2019) 17(1):143. doi: 10.1186/s12967-019-1895-2

165. Liu L, Zhu H, Liao Y, Wu W, Liu L, Liu L, et al. Inhibition of wnt/β-catenin pathway reverses multi-drug resistance and EMT in Oct4+/Nanog+ NSCLC cells. *BioMed Pharmacother* (2020) 127:110225. doi: 10.1016/j.biopha.2020.110225
Glossary

<table><tr><td>ACC</td><td>Acetyl CoA Carboxylase</td></tr><tr><td>aeTSA</td><td>Aberrantly expressed tumor specific antigen</td></tr><tr><td>AMP</td><td>Adenosine monophosphate</td></tr><tr><td>AMPK</td><td>AMP-activated protein kinase</td></tr><tr><td>ATF3</td><td>Activating transcription factor 3</td></tr><tr><td>ATF4</td><td>Activating transcription factor 4</td></tr><tr><td>ATP</td><td>Adenosine triphosphate</td></tr><tr><td>CAFs</td><td>Cancer associated fibroblasts</td></tr><tr><td>cGAMP</td><td>Cyclic di-guanosine-adenosine monophosphate</td></tr><tr><td>cGAS</td><td>Cyclic GMP-AMP synthase</td></tr><tr><td>COX-2</td><td>Cyclo-oxygenase-2</td></tr><tr><td>CRC</td><td>Colorectal cancer</td></tr><tr><td>CTLA-4</td><td>Cytotoxic T-lymphocyte associated protein 4</td></tr><tr><td>DC</td><td>Dendritic cell</td></tr><tr><td>DDR</td><td>DNA damage repair</td></tr><tr><td>dMMR</td><td>Deficient mismatch repair</td></tr><tr><td>DNA-PK</td><td>DNA-dependent protein kinase</td></tr><tr><td>DNMT1</td><td>DNA methyltransferase 1</td></tr><tr><td>dsDNA</td><td>double-stranded DNA</td></tr><tr><td>dsRNA</td><td>double stranded RNA</td></tr><tr><td>EGFR</td><td>Epidermal Growth Factor Receptor</td></tr><tr><td>ELR</td><td>Glutamate-Leucine-Arginine motif</td></tr><tr><td>ENPP1</td><td>Ectonucleotide pyrophosphatase/phosphodiesterase 1</td></tr><tr><td>ERK</td><td>Extracellular-signal related kinase</td></tr><tr><td>ERVs</td><td>Endogenous retroviruses</td></tr><tr><td>EZH2</td><td>Enhancer of zeste 2 polycomb repressive complex 2 subunit</td></tr><tr><td>FASN</td><td>Fatty acids synthase</td></tr><tr><td>Foxp3</td><td>Forkead box P3</td></tr><tr><td>G-CSF</td><td>Granulocyte-Colony Stimulating Factor</td></tr><tr><td>GLUT1</td><td>Glucose transporter 1</td></tr><tr><td>GM-CSF</td><td>Granulocyte-monocyte colony stimulating factor</td></tr><tr><td>HER-2</td><td>Human epithelial growth factor receptor-2</td></tr><tr><td>HIF-1α</td><td>Hypoxia-inducible factor-1α</td></tr><tr><td>MHC-I</td><td>Major histocompatibility complex-1</td></tr><tr><td>HK2</td><td>Hexokinase 2</td></tr><tr><td>HNRNPC</td><td>Heterogeneous nuclear ribonucleoprotein C</td></tr><tr><td>HNSCC</td><td>Head and neck squamous cell carcinoma</td></tr><tr><td>HO-1</td><td>Heme oxygenase-1</td></tr></table>

(Continued)

Continued

<table><tr><td>HRR-BER</td><td>Homologous recombination repair and base excision repair</td></tr><tr><td>HRR-MMR</td><td>Homologous recombination repair and mismatch repair</td></tr><tr><td>ICB</td><td>Immune checkpoint blockers</td></tr><tr><td>IDO-1</td><td>Indoleamine 2</td></tr><tr><td>3-dioxygenase-1</td><td></td></tr><tr><td>IFN</td><td>Interferon</td></tr><tr><td>IKKe</td><td>Inhibitor of NFkB kinase subunit epsilon</td></tr><tr><td>IL-6</td><td>Interleukin-6</td></tr><tr><td>IL-17</td><td>Interleukin-17</td></tr><tr><td>IRF1</td><td>Interferon regulatory factor 1</td></tr><tr><td>IRF3</td><td>Interferon regulatory factor 3</td></tr><tr><td>ISG</td><td>Interferon stimulated genes</td></tr><tr><td>JNK</td><td>Jun N-terminal kinase</td></tr><tr><td>KL</td><td>KRAS-LKB1 co-mutated</td></tr><tr><td>KP</td><td>KRAS-TP53 co-mutated</td></tr><tr><td>LDH-A</td><td>Lactate dehydrogenase-A</td></tr><tr><td>LINEs</td><td>Long interspersed nuclear elements</td></tr><tr><td>lncRNA</td><td>Long non-coding RNA</td></tr><tr><td>lncRNA-AS</td><td>Long non-coding RNA antisense</td></tr><tr><td>MAGE-A3</td><td>Melanoma-associated antigen family member 3</td></tr><tr><td>MAPK</td><td>Mitogen-Activated Protein Kinase</td></tr><tr><td>MDA5</td><td>Melanoma differentiation-associated gene 5</td></tr><tr><td>MDSCs</td><td>Myeloid-derived suppressor cells</td></tr><tr><td>MSH2</td><td>mutS homolog 2</td></tr><tr><td>MUC-1</td><td>Mucin-1</td></tr><tr><td>MSI<sup>h</sup>-CRC</td><td>Microsatellite-instability-high colorectal cancer</td></tr><tr><td>MSS-CRC</td><td>Microsatellite stable colorectal cancer</td></tr><tr><td>mTOR</td><td>mechanistic Target Of Rapamycin kinase</td></tr><tr><td>mTORC1</td><td>mTOR complex 1</td></tr><tr><td>NFkB</td><td>Nuclear factor kappa B</td></tr><tr><td>NK</td><td>Natural Killer</td></tr><tr><td>NRF2</td><td>Nuclear factor erythroid 2 related factor 2</td></tr><tr><td>NSAID</td><td>Non-steroidal anti-inflammatory drugs</td></tr><tr><td>NSCLC</td><td>Non-small cell lung cancer</td></tr><tr><td>NY-ESO-1</td><td>New York Esophageal cell carcinoma 1</td></tr><tr><td>ox-LDL</td><td>oxidized low-density-lipoproteins</td></tr><tr><td>PAP</td><td>Prostatic acid phosphatase</td></tr><tr><td>PD-1</td><td>Programmed cell death-1</td></tr><tr><td>PD-L1</td><td>Programmed cell death-ligand 1</td></tr><tr><td>PGE2</td><td>Prostaglandine-E2</td></tr></table>

(Continued)
Glossary

<table><tr><td>ACC</td><td>Acetyl CoA Carboxylase</td></tr><tr><td>aeTSA</td><td>Aberrantly expressed tumor specific antigen</td></tr><tr><td>AMP</td><td>Adenosine monophosphate</td></tr><tr><td>AMPK</td><td>AMP-activated protein kinase</td></tr><tr><td>ATF3</td><td>Activating transcription factor 3</td></tr><tr><td>ATF4</td><td>Activating transcription factor 4</td></tr><tr><td>ATP</td><td>Adenosine triphosphate</td></tr><tr><td>CAFs</td><td>Cancer associated fibroblasts</td></tr><tr><td>cGAMP</td><td>Cyclic di-guanosine-adenosine monophosphate</td></tr><tr><td>cGAS</td><td>Cyclic GMP-AMP synthase</td></tr><tr><td>COX-2</td><td>Cyclo-oxygenase-2</td></tr><tr><td>CRC</td><td>Colorectal cancer</td></tr><tr><td>CTLA-4</td><td>Cytotoxic T-lymphocyte associated protein 4</td></tr><tr><td>DC</td><td>Dendritic cell</td></tr><tr><td>DDR</td><td>DNA damage repair</td></tr><tr><td>dMMR</td><td>Deficient mismatch repair</td></tr><tr><td>DNA-PK</td><td>DNA-dependent protein kinase</td></tr><tr><td>DNMT1</td><td>DNA methyltransferase 1</td></tr><tr><td>dsDNA</td><td>double-stranded DNA</td></tr><tr><td>dsRNA</td><td>double stranded RNA</td></tr><tr><td>EGFR</td><td>Epidermal Growth Factor Receptor</td></tr><tr><td>ELR</td><td>Glutamate-Leucine-Arginine motif</td></tr><tr><td>ENPP1</td><td>Ectonucleotide pyrophosphatase/phosphodiesterase 1</td></tr><tr><td>ERK</td><td>Extracellular-signal related kinase</td></tr><tr><td>ERVs</td><td>Endogenous retroviruses</td></tr><tr><td>EZH2</td><td>Enhancer of zeste 2 polycomb repressive complex 2 subunit</td></tr><tr><td>FASN</td><td>Fatty acids synthase</td></tr><tr><td>Foxp3</td><td>Forkead box P3</td></tr><tr><td>G-CSF</td><td>Granulocyte-Colony Stimulating Factor</td></tr><tr><td>GLUT1</td><td>Glucose transporter 1</td></tr><tr><td>GM-CSF</td><td>Granulocyte-monocyte colony stimulating factor</td></tr><tr><td>HER-2</td><td>Human epithelial growth factor receptor-2</td></tr><tr><td>HIF-1α</td><td>Hypoxia-inducible factor-1α</td></tr><tr><td>MHC-I</td><td>Major histocompatibility complex-1</td></tr><tr><td>HK2</td><td>Hexokinase 2</td></tr><tr><td>HNRNPC</td><td>Heterogeneous nuclear ribonucleoprotein C</td></tr><tr><td>HNSCC</td><td>Head and neck squamous cell carcinoma</td></tr><tr><td>HO-1</td><td>Heme oxygenase-1</td></tr></table>

(Continued)

Continued

<table><tr><td>HRR-BER</td><td>Homologous recombination repair and base excision repair</td></tr><tr><td>HRR-MMR</td><td>Homologous recombination repair and mismatch repair</td></tr><tr><td>ICB</td><td>Immune checkpoint blockers</td></tr><tr><td>IDO-1</td><td>Indoleamine 2</td></tr><tr><td>3-dioxygenase-1</td><td></td></tr><tr><td>IFN</td><td>Interferon</td></tr><tr><td>IKKe</td><td>Inhibitor of NFkB kinase subunit epsilon</td></tr><tr><td>IL-6</td><td>Interleukin-6</td></tr><tr><td>IL-17</td><td>Interleukin-17</td></tr><tr><td>IRF1</td><td>Interferon regulatory factor 1</td></tr><tr><td>IRF3</td><td>Interferon regulatory factor 3</td></tr><tr><td>ISG</td><td>Interferon stimulated genes</td></tr><tr><td>JNK</td><td>Jun N-terminal kinase</td></tr><tr><td>KL</td><td>KRAS-LKB1 co-mutated</td></tr><tr><td>KP</td><td>KRAS-TP53 co-mutated</td></tr><tr><td>LDH-A</td><td>Lactate dehydrogenase-A</td></tr><tr><td>LINEs</td><td>Long interspersed nuclear elements</td></tr><tr><td>lncRNA</td><td>Long non-coding RNA</td></tr><tr><td>lncRNA-AS</td><td>Long non-coding RNA antisense</td></tr><tr><td>MAGE-A3</td><td>Melanoma-associated antigen family member 3</td></tr><tr><td>MAPK</td><td>Mitogen-Activated Protein Kinase</td></tr><tr><td>MDA5</td><td>Melanoma differentiation-associated gene 5</td></tr><tr><td>MDSCs</td><td>Myeloid-derived suppressor cells</td></tr><tr><td>MSH2</td><td>mutS homolog 2</td></tr><tr><td>MUC-1</td><td>Mucin-1</td></tr><tr><td>MSI<sup>h</sup>-CRC</td><td>Microsatellite-instability-high colorectal cancer</td></tr><tr><td>MSS-CRC</td><td>Microsatellite stable colorectal cancer</td></tr><tr><td>mTOR</td><td>mechanistic Target Of Rapamycin kinase</td></tr><tr><td>mTORC1</td><td>mTOR complex 1</td></tr><tr><td>NFkB</td><td>Nuclear factor kappa B</td></tr><tr><td>NK</td><td>Natural Killer</td></tr><tr><td>NRF2</td><td>Nuclear factor erythroid 2 related factor 2</td></tr><tr><td>NSAID</td><td>Non-steroidal anti-inflammatory drugs</td></tr><tr><td>NSCLC</td><td>Non-small cell lung cancer</td></tr><tr><td>NY-ESO-1</td><td>New York Esophageal cell carcinoma 1</td></tr><tr><td>ox-LDL</td><td>oxidized low-density-lipoproteins</td></tr><tr><td>PAP</td><td>Prostatic acid phosphatase</td></tr><tr><td>PD-1</td><td>Programmed cell death-1</td></tr><tr><td>PD-L1</td><td>Programmed cell death-ligand 1</td></tr><tr><td>PGE2</td><td>Prostaglandine-E2</td></tr></table>

(Continued)
Continued

<table><tr><td>PI3K</td><td>Phosphatidylinositol-3-kinase</td></tr><tr><td>PMN</td><td>Polymorphonuclear cells</td></tr><tr><td>POLD1</td><td>DNA polymerase delta 1</td></tr><tr><td>POLE</td><td>DNA polymerase epsilon</td></tr><tr><td>PTEN</td><td>Phosphatase and tensin homolog</td></tr><tr><td>RBPs</td><td>RNA binding proteins</td></tr><tr><td>RCC</td><td>Renal cell carcinoma</td></tr><tr><td>RIG-I</td><td>Retinoic acid-inducible gene I</td></tr><tr><td>SAM</td><td>S-adenosylmethionine</td></tr><tr><td>SASP</td><td>Senescence-associated secretory program</td></tr><tr><td>SCLC</td><td>Small cell lung cancer</td></tr><tr><td>SHP2</td><td>Src homology-2 domain containing phosphatase 2</td></tr><tr><td>SINEs</td><td>Short interspersed nuclear elements</td></tr><tr><td>STING</td><td>Stimulator of interferon genes</td></tr><tr><td>STK11</td><td>Serine/Threonine Kinase 11</td></tr><tr><td>TAAs</td><td>Tumor associated antigens</td></tr><tr><td>TBK1</td><td>Tank-Binding Kinase 1</td></tr><tr><td>TCA</td><td>Tricarboxylic acid</td></tr><tr><td>TCGA</td><td>The Cancer Genome Atlas</td></tr><tr><td>TCR</td><td>T-cell receptor</td></tr><tr><td>TEs</td><td>Transposable elements</td></tr><tr><td>TERT</td><td>Telomerase reverse transcriptase</td></tr><tr><td>TGF-β</td><td>Transforming Growth Factor-β</td></tr><tr><td>Th1</td><td>T-helper-I</td></tr><tr><td>TKI</td><td>Tyrosine kinase inhibitors</td></tr><tr><td>TLR3</td><td>Toll-like receptor 3</td></tr><tr><td>TLS</td><td>Tertiary-lymphoid structures</td></tr><tr><td>TMB</td><td>Tumor mutation burden</td></tr><tr><td>TME</td><td>Tumor microenvironment</td></tr><tr><td>TNB</td><td>Tumor neoantigen burden</td></tr><tr><td>TNF</td><td>Tumor Necrosis Factor</td></tr><tr><td>TNM</td><td>Tumor Node Metastasis</td></tr><tr><td>Treg</td><td>Regulatory T lymphocytes</td></tr><tr><td>TSA</td><td>Tumor-specific antigens</td></tr><tr><td>VEGF</td><td>Vascular Endothelial Growth Factor</td></tr><tr><td>WT</td><td>Wild type</td></tr></table>
Continued

<table><tr><td>PI3K</td><td>Phosphatidylinositol-3-kinase</td></tr><tr><td>PMN</td><td>Polymorphonuclear cells</td></tr><tr><td>POLD1</td><td>DNA polymerase delta 1</td></tr><tr><td>POLE</td><td>DNA polymerase epsilon</td></tr><tr><td>PTEN</td><td>Phosphatase and tensin homolog</td></tr><tr><td>RBPs</td><td>RNA binding proteins</td></tr><tr><td>RCC</td><td>Renal cell carcinoma</td></tr><tr><td>RIG-I</td><td>Retinoic acid-inducible gene I</td></tr><tr><td>SAM</td><td>S-adenosylmethionine</td></tr><tr><td>SASP</td><td>Senescence-associated secretory program</td></tr><tr><td>SCLC</td><td>Small cell lung cancer</td></tr><tr><td>SHP2</td><td>Src homology-2 domain containing phosphatase 2</td></tr><tr><td>SINEs</td><td>Short interspersed nuclear elements</td></tr><tr><td>STING</td><td>Stimulator of interferon genes</td></tr><tr><td>STK11</td><td>Serine/Threonine Kinase 11</td></tr><tr><td>TAAs</td><td>Tumor associated antigens</td></tr><tr><td>TBK1</td><td>Tank-Binding Kinase 1</td></tr><tr><td>TCA</td><td>Tricarboxylic acid</td></tr><tr><td>TCGA</td><td>The Cancer Genome Atlas</td></tr><tr><td>TCR</td><td>T-cell receptor</td></tr><tr><td>TEs</td><td>Transposable elements</td></tr><tr><td>TERT</td><td>Telomerase reverse transcriptase</td></tr><tr><td>TGF-β</td><td>Transforming Growth Factor-β</td></tr><tr><td>Th1</td><td>T-helper-I</td></tr><tr><td>TKI</td><td>Tyrosine kinase inhibitors</td></tr><tr><td>TLR3</td><td>Toll-like receptor 3</td></tr><tr><td>TLS</td><td>Tertiary-lymphoid structures</td></tr><tr><td>TMB</td><td>Tumor mutation burden</td></tr><tr><td>TME</td><td>Tumor microenvironment</td></tr><tr><td>TNB</td><td>Tumor neoantigen burden</td></tr><tr><td>TNF</td><td>Tumor Necrosis Factor</td></tr><tr><td>TNM</td><td>Tumor Node Metastasis</td></tr><tr><td>Treg</td><td>Regulatory T lymphocytes</td></tr><tr><td>TSA</td><td>Tumor-specific antigens</td></tr><tr><td>VEGF</td><td>Vascular Endothelial Growth Factor</td></tr><tr><td>WT</td><td>Wild type</td></tr></table>