tbuckley/cabot-search huggingface dataset:
A phase Ib/II study of PXD101 alone and in combination with 5-fluorouracil in patients with advanced solid tumors
Authors: D. W. Northfelt, R. F. Marschke, E. Bonnem, C. E. Ooi, R. Gerwien, T. Hawthorne, A. Clarke, P. Buhl-Jensen, D. Von Hoff, J. Grem
Journal: Journal of Clinical Oncology (2007)

3501 Background: PXD101 is a hydroxamate HDAC inhibitor that has broad anti-neoplastic activity in vivo and in vitro. Preclinical data showing PXD101 down-regulation of thymidylate synthase (TS), an in vivo target of 5-fluorouracil (5-FU) provide a rationale for combination of PXD101 with 5-FU. Methods: This is a phase Ib/II trial of PXD101 plus 5-FU in patients with advanced solid tumors, with dose escalation to establish the maximum tolerated dose (MTD) and an expansion at the MTD in colorectal cancer (CRC) patients. Patients (pts) must be = 18 yrs, have measurable disease, and had disease progression after standard chemotherapy. PXD101 was administered as a 30-min IV infusion on Days 1–5 of a 3-wk cycle. 5-FU was administered from cycle 2 on, as a continuous 96-hr IV infusion starting on Day 2 of the same 3-wk cycle. The primary endpoints were safety, and effect of belinostat on TS expression in patients’ tumors. Dose-limiting toxicities (DLTs) were PXD101-related = Gr 3 non-hematologic or Gr 4 hematologic toxicities. Expression of TS mRNA was measured by RTQ-PCR. Results: Twenty pts have been treated for a median of 2 cycles (range 1–8). Cohorts of 3–6 pts were tested at 5 dose levels of PXD101/5-FU (mg/m 2 /d): 300/250, 600/250, 1,000/250, 1,000/500, and 1,000/1,000. Two pts did not complete cycle 2, and one pt at the 600/250 dose level received 1,000 mg/m 2 /d 5-FU. There were no DLTs in the first 4 dose cohorts; the 5 th cohort is ongoing. In the first 4 dose cohorts (17 pts), the most frequent AEs were fatigue, nausea/vomiting, dysgeusia, dehydration, constipation, edema, anorexia and anemia. There were 2 Gr 4 AEs (pulmonary embolism, bacteremia); Gr 3 AEs in = 2 pts were fatigue and dehydration. All Gr 3/4 events were assessed as not related to PXD101. One pt with stage IV CRC treated at 600/1,000 mg/m 2 /d PXD101/5-FU had stable disease (SD) for 8 cycles, and one pt with stage IV esophageal cancer treated at the 1,000/250 mg/m 2 /d dose had SD for 4 cycles. Conclusions: PXD101 in combination with 5-FU has been well tolerated up to 1,000/500 mg/m 2 /d PXD101/5-FU. The study is ongoing and data from the MTD expansion part, including effect of PXD101 on tumor TS expression, will be presented. No significant financial relationships to disclose.
HIF-1a Pathway, As a Signal Funnel for Genetic, Epigenetic, and Metabolic Aberrations, Is Sufficient and Essential for MDS Development
Authors: Yoshihiro Hayashi, Yue Zhang, Xiaomei Yan, Kwangmin Choi, Goro Sashida, Yunzhu Dong, Zefeng Xu, Lingyun Wu, Aili Chen, Xiujuan Sun, Andre Olsson, Hironori Harada, Lee-Yung Shih, William Tse, James Bridges, David P Witte, Qianfei Wang, Michael A. Caligiuri, H. Leighton Grimes, Stephen D. Nimer, Zhijian Xiao, Gang Huang
Journal: Blood (2015)
GW26-e2368 Association of C5L2 Genetic Polymorphisms and Prognosis of Coronary Artery Disease in Xinjiang Han and Uygur Population, China
Authors: Yingying Zheng, Xiang Xie, Yining Yang, Zhenyan Fu, Xiaomei Li, Shuo Pan, Dilare Adi, Bangdang Chen, Fen Liu, Yitong Ma
Journal: Journal of the American College of Cardiology (2015)
Outcome of Second Line Treatment in Patients with Chronic Lymphocytic Leukemia Did Not Improve 2002-2013: A Population-Based Study from a Well-Defined Geographic Region
Authors: Anna Asklid, Agnes Mattsson, Einar Björgvinsson, Maria Winqvist, Sandra Eketorp Sylvan, Frans Søltoft, Johanna Repits, Joris Diels, Anders Österborg, Lotta Hansson
Journal: Blood (2015)
Changes in iron parameters in patients (pts) with chemotherapy-induced anemia (CIA) receiving darbepoetin alfa (DA) every 3 weeks with and without intravenous iron supplementation
Authors: T. Suto, J. F. Vansteenkiste, T. Mossman, T. Pinter
Journal: Journal of Clinical Oncology (2007)

19621 Background: There is growing interest in the use of intravenous (IV) iron supplementation in pts receiving erythropoiesis- stimulating agents (ESAs). We present an exploratory analysis of iron parameters in pts with CIA enrolled in a phase IIIb, randomized, open- label, study of DA administered with either IV iron or oral/no iron. Methods: Eligible pts had a non-myeloid malignancy and CIA (baseline Hb &lt; 11g/dL). Pts received DA 500 mcg every 3 weeks (Q3W) using the Aranesp (darbepoetin alfa) prefilled SureClick autoinjector. Pts were randomly allocated (1:1) to receive either DA + 200 mg IV iron (200 mg Q3W with DA Q3W or two 100 mg doses within 3 weeks) or DA + oral/no iron. Randomization was stratified by tumor type and baseline Hb (&lt; or = 10 g/dL). The primary endpoint was % pts achieving a hematopoietic response (Hb = 12 g/dL or increase = 2 g/dL). Results: 396 randomized pts received 1 dose of DA (IV-iron arm = 200; oral/no-iron arm = 196). Mean (SD) age was 61.0 (11.5) yrs; 61% (n = 240) were women; 28% (n = 111) had lung/gynecological tumors. Pt demographics were similar between arms. 44 (11%) pts had baseline iron deficiency (TSAT &lt; 15%; serum ferritin &lt; 100 μg/L); 5 (2%) in the IV iron arm and 23 (12%) in the oral/no-iron arm developed it. 141 (36%) pts had baseline functional iron deficiency (serum iron &lt; 60 μg/dL; serum ferritin &gt; 20 μg/L; TSAT &lt; 20%); 54 (27%) in the IV arm and 67 (35%) in the oral/no-iron arm developed it. See table for iron parameters. Improved Hb-based responses in the IV-iron arm will be presented. Conclusions: Pts who received DA Q3W + IV iron appeared less likely to develop iron deficiency; iron deficiency may reduce responsiveness to ESAs. These pts also appeared to have a larger increase in mean serum ferritin levels. In contrast, mean serum iron, %TSAT, total iron binding capacity, and reticulocytes appeared to be similar in the 2 arms for most of the study period, suggesting that these iron parameters are not influenced by IV iron. No significant financial relationships to disclose. [Table: see text]
Microrna-150 Regulates STAT5b Levels in Juvenile Myelomonocytic Leukemia (JMML)
Authors: Pier Paolo Leoncini, Alice Bertaina, Dimitrios Papaioannou, Christian Flotho, Riccardo Masetti, Silvia Bresolin, Giuseppe Menna, Nicola Santoro, Marco Zecca, Giuseppe Basso, Giovanni Nigita, Sara Pagotto, Katia D'Ovidio, Rossella Rota, Carlo M. Croce, Charlotte Marie Niemeyer, Franco Locatelli, Ramiro Garzon
Journal: Blood (2015)
Risk of relapse with imatinib (IM) discontinuation at 5 years in advanced GIST patients: Results of the prospective BFR14 randomized phase III study comparing interruption versus continuation of IM at 5 years of treatment: A French Sarcoma Group Study.
Authors: I. L. Ray-Coquard, N. Bin Bui, A. Adenis, M. Rios, F. Bertucci, S. Chabaud, D. Pérol, J. Blay, A. Le Cesne
Journal: Journal of Clinical Oncology (2010)

10032 Background: We previously showed in the BFR14 study that IM interruption results in increased risk of disease progression (PD) after 1 and 3 years (yr) in non progressing patients (pts). The impact of IM discontinuation on progression free survival (PFS) in responding pts at 5 yrs is unknown. Methods: This prospective multicenter BFR14 study was initiated in 06/02 and completed inclusion in 05/09. After 1, 3, and 5 yrs of IM 400 mg/day, pts free from PD were randomly offered to continue (C arm) or Stop (S arm) IM. Pts allocated to the S arm had to restart IM (same dose) in case of PD. Primary endpoint was PFS. A Bayesian model was implemented for this part of the BFR14 study. Results: Overall, 434 pts were included in the BFR14 study. Fifty-eight (n=26 vs. n=32), 50 (n=25 vs. n=25) and 21 (n=11 vs. n=10) non progressive pts at were randomized at 1, 3 or 5 yrs in the S vs C arms. The 2 yr-PFS were 13% and 16% in the S arms after 1 and 3 years of treatment compared to 62% and 80% in the C arms after 1 and 3 yrs of IM respectively. 21 pts responding to IM at 5 yrs and not previously randomized in the 1 or 3 yrs S arms were randomized after 5 yrs of IM. After a median follow-up of 12 months (6.8-15.1) from randomization, 5 of the 11 pts randomized in the S arm have relapsed while no relapse was observed among the 10 pts randomized in the C arm (p=0.035) The results compare favorably to the 1 yr and 3 yrs cohort for the C arms: 1 year after randomization at 1, 3, and 5 years, the relapse rate was 20% in the 1 yr C cohort, vs. 8% in the 3 yrs C cohort, vs. 0% in the 5-yrs C cohort. IM reintroduction in the I arm (at 1, 3 or 5 yrs) after a reprogression allowed a tumor control in all evaluable pts to date. Conclusions: Despite long term tumor control, IM interruption at 5 yrs resulted in a higher rate of progression than imatinib maintenance in patients with advanced GIST in this randomized study. IM has to be given continuously until PD or intolerance in the population of non progressing advanced or metastatic GIST. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer, GlaxoSmithKline, Novartis, Pfizer, PharmaMar, Roche, sanofi-aventis Chugai Pharma, GlaxoSmithKline, Novartis, Novo Nordisk, Pfizer, PharmaMar, Roche Merck, Novartis, Pfizer, Roche Novartis, PharmaMar
Abstract 704: Long Term Prognostic Value of Stress Perfusion CMR Study for the Prediction of Cardiovascular Death and Non Fatal Acute Myocardial Infarction in 1009 Asian Patients
Authors: Tairo Kurita, Hajime Sakuma, Hiroshi Nakajima, Shingo Kato, Hideki Miyagi, Shiro Nakamori, Kakuya Kitagawa, Katsuya Onishi, Mashio Nakamura, Masaaki Ito
Journal: Circulation (2009)

Background: Recent studies demonstrated the prognostic importance of stress perfusion MRI and late gadolinium enhanced (LGE) MRI in patients with suspected coronary artery disease (CAD). However, CAD rates and risk levels in Asian population have been shown to be lower than those in western countries. In the current study, we determined the long term (up to 10 years) prognostic value of CMR study with vasodilator stress in a large number of Asian patients.

Methods: We studied 1009 patients with known or suspected CAD who underwent both stress perfusion MRI and late gadolinium enhanced (LGE) MRI. Stress-induced ischemia and myocardial scar were qualitatively determined on CMR. Major adverse cardiac event (MACE) was defined as cardiovascular death and non fatal acute myocardial infarction (MI).

Results: During average follow-up time of 40 months (range, 6 to 120 months), presence of LGE predicted patients outcome with hazard ratio of 2.0 (95% CI 1.2–3.5, P<0.01). When stress perfusion MRI and LGE MRI were combined, abnormal stress CMR was a significant negative prognostic factor of MACE with a high hazard ratio of 5.2 (95% CI 2.2–12.0, P<0.001). Normal stress CMR was associated with lower event rate per year (0.3%) as compared with that by normal LGE alone (1.3%). (Figure 1[⇓][1])

Conclusions: Combined assessment of stress induced ischemia and myocardial scar with stress CMR provided improved prognostic value when compared with LGE MRI alone in Asian population with known or suspected CAD. Patients with normal stress CMR had lower risk of cardiovascular death and MACE.



   ![][2] 

Figure 1.  
Kaplan-Meier survival curves based on presence of LGE alone (left) and any abnormality on stress/LGE CMR (right).

 [1]: #graphic-1
 [2]: /embed/graphic-1.gif
Pretransplant NPM1 -MRD Levels Predict Outcome after Allogeneic Stem Cell Transplantation in Adult Patients with Acute Myeloid Leukemia
Authors: Sabine Kayser, Axel Benner, Christian Thiede, Uwe Martens, Josef Huber, Peter Stadtherr, Johannes W.G. Janssen, Christoph Röllig, Michael J. Uppenkamp, Tilmann Bochtler, Ute Hegenbart, Gerhard Ehninger, Anthony D. Ho, Peter Dreger, Alwin Kraemer
Journal: Blood (2015)
The Central Nervous System Is a Target Organ of Acute Graft-Versus-Host Disease
Authors: Steffen Hartrampf, Jarrod A Dudakov, Linda K Johnson, Odette M Smith, Jennifer J Tsai, Alan M Hanash, Natalie V Singer, Mallory L West, Bing F Liu, Miklos Toth, Marcel R.M. van den Brink
Journal: Blood (2011)
Screening for Paroxysmal Nocturnal Hemoglobinuria (PNH) in Patients with Cytopenia and Suspected Myelodysplasia Using the Fluorochrome-Conjugated Derivative of Aerolysin, FLAER
Authors: Wolfgang Kern, Claudia Haferlach, Susanne Schnittger, Torsten Haferlach
Journal: Blood (2008)
Extended-spectrum β-lactamase- and pAmpC-producing Enterobacteriaceae among the general population in a livestock-dense area
Authors: C.C.H. Wielders, A.H.A.M. van Hoek, P.D. Hengeveld, C. Veenman, C.M. Dierikx, T.P. Zomer, L.A.M. Smit, W. van der Hoek, D.J. Heederik, S.C. de Greeff, C.B.M. Maassen, E. van Duijkeren
Journal: Clinical Microbiology and Infection (2016)
The CD38-Positive and CD38-Negative Subsets of CD34(high)-Positive Primary Acute Myeloid Leukemia Blasts Differ Considerably in the Expression of Immune Recognition Molecules
Authors: Eva Distler, Anna Jürchott, Abdo Konur, Astrid Schneider, Eva M. Wagner, Christoph Huber, Ralf G. Meyer, Wolfgang Herr
Journal: Blood (2008)
GW26-e5437 Association of elevated apoA-I glycation and reduced HDL-associated paraoxonase 1, 3 activity, and their interaction with angiographic severity of coronary artery disease in patients with type 2 diabetes mellitus
Authors: Ying Shen, Fenghua Ding, Jiateng Sun, Ruiyan Zhang, Qi Zhang, Qiujing Chen, Lin Lu, Weifeng Shen
Journal: Journal of the American College of Cardiology (2015)
Inflammatory bowel disease is associated with hidradenitis suppurativa: Results from a multicenter cross-sectional study
Authors: Inge E. Deckers, Farida Benhadou, Marjolein J. Koldijk, Veronique del Marmol, Barbara Horváth, Jurr Boer, Hessel H. van der Zee, Errol P. Prens
Journal: Journal of the American Academy of Dermatology (2016)
AT7519, a Potent CDK Inhibitor, Is Active in Leukemia Models and Primary CLL Patient Samples.
Authors: Matthew S. Squires, Ruth E. Feltell, Victoria Lock, Donna M. Smith, Jon E. Lewis, Jacqueline Higgins, Murray Yule, Neil T. Thompson, Laurence Cooke, Kimiko D. Croce, Wenqing Qi, John F. Lyons, Daruka Mahadevan
Journal: Blood (2007)
Total Therapy (TT) Studies For Gene Expression Profiling (GEP)-Defined High-Risk Multiple Myeloma
Authors: Christoph Heuck, Frits van Rhee, Alan Mitchell, Adam Rosenthal, Sarah Waheed, Nathan M Petty, Clyde Bailey, Ryan Williams, Ryan van Laar, Susan B. Panozzo, Jeffrey Sawyer, John Crowley, Bart Barlogie
Journal: Blood (2013)
Phase II Trial of Bortezomib Combined with Weekly Doxorubicin and Oral Dexamethasone for Relapsed or Refractory Multiple Myeloma (MM): Effect of NF-κB Activation on Response.
Authors: Natalie S. Callander, Shigeki Miyamoto, Brad Kahl, Stephanie Markovina, Martha Raschko, Jae Werndl, Catherine Leith, Alice McCoy
Journal: Blood (2006)
GW26-e1250 Incidence, Risk Factors, and In-hospital Outcomes of Acute Kidney Injury Before Thoracic Endovascular Aneurysm Repair in Patients With Type B Acute Aortic Dissection
Authors: Xiao Wang, Hongmei Ren, Chunyan Hu, Bin Que, Hui Ai, Chunmei Wang, Lizhong Sun, Shaoping Nie
Journal: Journal of the American College of Cardiology (2015)
Effect of bortezomib on ER stress and killing of cisplatin-resistant U2OS osteosarcoma cell line.
Authors: W. Zhao, M. Callaghan, A. Fribley, Y. Ravindranath, Z. J. Wang
Journal: Journal of Clinical Oncology (2010)

9566 Background: Proteasome inhibitor bortezomib is a new class of antineoplastic agents. We believe that the conclusion from previous sarcoma trial that bortezomib was not effective in the treatment of sarcomas should not apply to osteosarcoma since the treatment arm including osteosarcoma was prematurely closed because of low accrual rate. We have previously reported that high level of MKP-1 was associated with cisplatin resistance in osteosarcoma cell lines. Since bortezomib has been reported to increase MKP-1 expression, we investigated the effect of bortezomib treatment on cisplatin sensitivity. Methods: U2OS and P16T osteosarcoma cell lines and mouse embryonic fibroblasts (MEFs) derived from target gene knockout (KO) mice of ATF-4, CHOP, IRE-1 and eIF2α and their paired wild type controls were used in this study. Results: Treatment with bortezomib indeed increased MKP-1 level in U2OS osteosarcoma cell line, but increase in cisplatin resistance was not observed, suggesting that increase in MKP-1 alone may not be adequate to induce cisplatin resistance. In contrast, concomitant exposure of U2OS cells to sub-therapeutic dose of bortezomib and therapeutic dose of cisplatin, which were both minimally cytotoxic when used alone, resulted in a striking increase in cytotoxicity, suggesting that bortezomib interacts synergistically with cisplatin in killing the osteosarcoma cells. Furthermore, bortezomib was more effective in killing cisplatin resistant U2OS than cisplatin sensitive P16T cells, and this increase in bortezomib sensitivity was in parallel with increased apoptosis and enhanced JNK activation in U2OS over P16T cells. While the most striking protective effect was observed in the CHOP K/O MEFs, which were almost completely protected from the bortezomib induced cell death, ATF-4 and IRE1a K/O also diminished the bortezomib cytotoxicity. In contrast, eIF2a K/O significantly enhanced the bortezomib lethality. Conclusions: The results support that bortezomib induced increase in ER stress indeed leads to increased cell death, and could be an effective novel agent in the treatment of cisplatin resistant osteosarcoma. No significant financial relationships to disclose.
A Single Nucleotide Polymorphism in CD19 Defines a Novel Target for Immunotherapy of B Cell Malignancies with CD4+ Cytotoxic T Cells.
Authors: Robbert M. Spaapen, Henk M. Lokhorst, Kelly van den Oudenalder, Brith Otterud, Harry Dolstra, Mark Leppert, Monique C. Minnema, Andries C. Bloem, Tuna Mutis
Journal: Blood (2007)
Abstract A15: Mechanisms of CD8+ T cell immunosuppression in triple negative breast cancer
Authors: Tina Gruosso, Mathieu Gigoux, Nicholas Bertos, Sadiq Saleh, Atilla Omeroglu, Dongmei Zuo, Hong Zhao, Margarita Souleimanova, Valerie Weaver, Sarkis Meterissian, Michael Hallett, Morag Park
Journal: Cancer Research (2016)

Abstract Triple negative breast cancer (TNBC), defined as tumors lacking expression of the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), are especially difficult to treat effectively. While ER+ and HER2+ breast cancer subtypes can be treated with Tamoxifen and Herceptin, respectively, there are no targeted therapies for TNBC patients. Furthermore, while only 20-30% of TNBC patients respond to chemotherapy in the neoadjuvant setting, overall outcome remains poor for non-responding patients. However, mounting evidence suggests that immune-checkpoint inhibitor immunotherapies may be especially promising for TNBC patients. We and others have shown that the presence of CD8+ T cells, a crucial component of the cytotoxic arm of the adaptive immune response, is a sign of good clinical outcome in TNBC patients. However, good outcome only correlates with CD8+ T cell invasion of the tumor parenchyma. Here we show that some patients have an accumulation of CD8+ T cells in the surrounding tumor-associated stroma, but not the tumor epithelium, and these patients responded as poorly as patients with no CD8+ T cells at all. Yet how cancer associated fibroblasts (CAFs), a dominant cell type of the tumor-associated stroma, affects CD8+ T cell invasion into the tumor epithelium is still poorly understood. To identify potential stroma-dependent mechanisms that potentiate or inhibit CD8+ T cells invasion into the tumor epithelium, we performed gene expression profiling of laser-capture microdissected tumor-associated stroma (and matched epithelium) from 56 TNBC cases. Here we identify several key stromal features that may explain the accumulation of CD8+ T cells outside of the tumor epithelium. Preliminary data by immunohistochemistry and immunofluorescence validate some key stromal features and decipher the implication of other immune cell types in CD8+ T cells lack of tumor epithelium infiltration. These key stromal features that impair CD8+ T cell infiltration into the tumor in some patients might explain the relative low efficiency of immunotherapies in TNBC patients (20% of patients respond). One could speculate that targeting these key stromal features would allow a significant CD8+ T cell infiltration into the tumor and thus sensitize patients to immunotherapies. Citation Format: Tina Gruosso, Mathieu Gigoux, Nicholas Bertos, Sadiq Saleh, Atilla Omeroglu, Dongmei Zuo, Hong Zhao, Margarita Souleimanova, Valerie Weaver, Sarkis Meterissian, Michael Hallett, Morag Park. Mechanisms of CD8+ T cell immunosuppression in triple negative breast cancer. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr A15.
Cell-Cell Communication Between Multiple Myeloma (MM) Cells and Cord Blood Derived NK Cells (CB-NK) Regulates Both Tumor Cell Death and Tumor Cell Survival
Authors: Beatriz Martin-Antonio, Erica Serrano, Guillermo Suñe, Lorena Perez, Marcos Calderón, Jose María Estanyol, Amer Najjar, Clara Bueno, Carlos Fernandez de Larrea, Alvaro Urbano-Ispizua
Journal: Blood (2015)
Antitumor adaptive immunity remains intact following inhibition of autophagy and antimalarial treatment
Authors: Hanna Starobinets, Jordan Ye, Miranda Broz, Kevin Barry, Juliet Goldsmith, Timothy Marsh, Fanya Rostker, Matthew Krummel, Jayanta Debnath
Journal: Journal of Clinical Investigation (2016)

The rising success of cancer immunotherapy has produced immense interest in defining the clinical contexts that may benefit from this therapeutic approach. To this end, there is a need to ascertain how the therapeutic modulation of intrinsic cancer cell programs influences the anticancer immune response. For example, the role of autophagy as a tumor cell survival and metabolic fitness pathway is being therapeutically targeted in ongoing clinical trials that combine cancer therapies with antimalarial drugs for the treatment of a broad spectrum of cancers, many of which will likely benefit from immunotherapy. However, our current understanding of the interplay between autophagy and the immune response remains incomplete. Here, we have evaluated how autophagy inhibition impacts the antitumor immune response in immune-competent mouse models of melanoma and mammary cancer. We observed equivalent levels of T cell infiltration and function within autophagy-competent and -deficient tumors, even upon treatment with the anthracycline chemotherapeutic doxorubicin. Similarly, we found equivalent T cell responses upon systemic treatment of tumor-bearing mice with antimalarial drugs. Our findings demonstrate that antitumor adaptive immunity is not adversely impaired by autophagy inhibition in these models, allowing for the future possibility of combining autophagy inhibitors with immunotherapy in certain clinical contexts.