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BackgroundImmunotherapy in microsatellite stable colorectal or pancreatic cancer has not shown promising results. It has been hypothesized that targeting immunosuppressive molecules like SDF1-alpha/CXCL12 could contribute to immunotherapy and animal models showed promising results on T cell activation and migration in combination with immune checkpoint inhibition.MethodsHere, we describe the successful application of anti-CXCL12 (NOX-A12) in patients with advanced stage pretreated metastatic colorectal and pancreatic cancer (OPERA trial). The treatment consisted of 2 weeks of anti-CXCL12 monotherapy with NOX-A12 followed by combination therapy with pembrolizumab (n=20 patients) until progression or intolerable toxicity had occurred.ResultsThe treatment was safe and well tolerated with 83.8% grade I/II, 15.5% grade III and 0.7% grade V adverse events. Of note, for a majority of patients, time on trial treatment was prolonged compared with their last standard treatment preceding trial participation. Systematic serial biopsies revealed distinct patterns of modulation. Tissue and clinical responses were associated with Th1-like tissue reactivity upon CXCL12 inhibition. A downregulation of a cytokine cassette of interleukin (IL)-2/IL-16/CXCL-10 was associated with tumor resistance and furthermore linked to a rare, CXCL12-associated CD14+CD15+promonocytic population. T cells showed aggregation and directed movement towards the tumor cells in responding tissues. Serum analyses detected homogeneous immunomodulatory patterns in all patients, regardless of tissue responses.ConclusionsWe demonstrate that the combination of CXCL12 inhibition and checkpoint inhibition is safe and grants further exploration of synergistic combinatorial strategies.

Induction of anti-tumor immunity in pancreatic ductal adenocarcinoma (PDA) is an unresolved challenge. Systematic investigation of the microenvironment of primary pancreatic tumors revealed a role of endocrine Langerhans islets in the coordination of immune activation. We found that intratumoral β-cells, regulated via STAT3, secrete C-C motif chemokine ligand 27 (CCL27) and thereby promote a TH1 phenotype in the microenvironment resulting in an enhanced T cell infiltration and prolonged patient survival. The local effect can be abrogated in a patient-based human explant model by inhibition of the CCL27 receptor CCR10. This defense mechanism is paralleled by an impaired metabolic function of Langerhans islets with reduced insulin levels resulting in a dysregulation of glycemic control in patients. Based on these findings, screening of PDA cases (n= 2264) led to the identification of type 2 diabetes mellitus (T2DM) and extractable glycated haemoglobin (HbA1c) levels as response markers for neoadjuvant chemotherapy with fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX). Collectively these data provide insights into the interconnection of T2DM and PDA, and link declining glycemic control to therapeutic efficacy, which can be utilized as a tool for clinical decision-making and improve patient management.

Background Ovarian cancer metastasis occurs by direct multifocal seeding in the peritoneum as well as by migration through the lymphatic system. High grade ovarian carcinoma patients present with distant metastases. Significant risk factors for the development of those are stage, grade, and lymph node involvement. An increase of the number of lymphatic vessels is shown in ovarian tumors and these vessels seem implicated in tumor progression. While the tropism of ovarian cancer cells for fat is well described, the potential impact of a fatty microenvironment on the dissemination of tumor cells via lymphatic vessels has, to our knowledge, never been investigated yet. In this study, we examined the effect of omental fat on lymphangiogenesis in ovarian carcinoma. Materials and Methods To examine the effect of omental fat on lymphangiogenesis in OC we used a cohort of 80 human specimens. We analysed lymphatic vessels histologically with D2-40 and Lyve-1 markers. We also developed a healthy fat tissue explant culture model and treated explants with ascites of patient with OC before analysis. We analysed by fluorescence stainings the co expression of adipose derived stem cells (ASCs) and lymphatic markers in these explants. Results We observed a higher density of tumor-associated vessels, especially lymphatic vessels in OC in contact with the omentum; mainly localized along the adipose tissue. We also measured a higher secretion of VEGF-C in tissues with fat compared to tissues without fat. Healthy fat tissues treated with ascites show an increase of number of ASCs, some of them express lymphatic markers such as D2-40 and Lyve-1. In a clinical trial of patients with OC treated by Bevacizumab, we observed a decrease of the number of lymphatic vessels in correlation with a decrease of the inflammation around the fat tissue. Discussion We saw an increase in the number of lymphatic vessels in ovarian carcinoma infiltrating fat. These vessels are principally distributed around the fat. We also observed an increase of proliferating ASC expressing lymphatic marker in fat explants treated with ascites. In a clinical trial of patients treated with Bevacizumab, we see a decrease of the lymphatic vessels. This decrease is linked with a decrease in the number of Inflammatory cells. These results together show that the fat tissue can play an important role in the lymphangiogenesis in the ovarian carcinoma. Furthermore, in the dissemination of metastasis through the body. We will next investigate the mechanisms underlying this phenomenon and try to understand all factors implicated in this process. Disclosure Information B.M.A. Lenoir: None. V. Starrach: None. D. Ferber: None. M. Suarez-Carmona: None. S. Schott: None. I. Zornig: None. D. Jager: None. N. Halama: None.

Solid tumors are rich ecosystems of numerous different cell types whose interactions lead to immune escape and resistance to immunotherapy in virtually all patients with metastatic cancer. Here, we have developed a 3D model of human solid tumor tissue that includes tumor cells, fibroblasts, and myeloid and lymphoid immune cells and can represent over a million cells over clinically relevant timeframes. This model accurately reproduced key features of the tissue architecture of human colorectal cancer and could be informed by individual patient data, yielding in silico tumor explants. Stratification of growth kinetics of these explants corresponded to significantly different overall survival in a cohort of patients with metastatic colorectal cancer. We used the model to simulate the effect of chemotherapy, immunotherapies, and cell migration inhibitors alone and in combination. We classified tumors according to tumor and host characteristics, showing that optimal treatment strategies markedly differed between these classes. This platform can complement other patient-specific ex vivo models and can be used for high-throughput screening of combinatorial immunotherapies. Significance: This patient-informed in silico tumor growth model allows testing of different cancer treatment strategies and immunotherapies on a cell/tissue level in a clinically relevant scenario. Cancer Res; 78(17); 5155–63. ©2018 AACR.

OncoImmunology 8(9), e1626193 (2019). doi:10.1080/2162402X.2019.1626193, Published by Taylor & Franics, Abingdon

The immune response influences the clinical course of colorectal cancer (CRC). Analyzing the invasive margin of human CRC liver metastases, we identified a mechanism of immune cell exploitation by tumor cells. While two distinct subsets of myeloid cells induce an influx of T cells into the invasive margin via CXCL9/CXCL10, CCL5 is produced by these T cells and stimulates pro-tumoral effects via CCR5. CCR5 blockade in patient-derived functional in vitro organotypic culture models showed a macrophage repolarization with anti-tumoral effects. These anti-tumoral effects were then confirmed in a phase I trial with a CCR5 antagonist in patients with liver metastases of advanced refractory CRC. Mitigation of tumor-promoting inflammation within the tumor tissue and objective tumor responses in CRC were observed.

Lymphoid and myeloid cells are abundant in the tumor microenvironment, can be quantified by immunohistochemistry and shape the disease course of human solid tumors. Yet, there is no comprehensive understanding of spatial immune infiltration patterns (‘topography’) across cancer entities and across various immune cell types. In this study, we systematically measure the topography of multiple immune cell types in 965 histological tissue slides from N = 177 patients in a pan-cancer cohort. We provide a definition of inflamed (‘hot’), non-inflamed (‘cold’) and immune excluded patterns and investigate how these patterns differ between immune cell types and between cancer types. In an independent cohort of N = 287 colorectal cancer patients, we show that hot, cold and excluded topographies for effector lymphocytes (CD8) and tumor-associated macrophages (CD163) alone are not prognostic, but that a bivariate classification system can stratify patients. Our study adds evidence to consider immune topographies as biomarkers for patients with solid tumors.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of death from cancer, with a 5-year survival of less than 8%. To date, the therapeutic approaches are chemotherapy regimens. Despite promising data from various preclinical models, new immunotherapeutic agents like checkpoint inhibitors (CPI), vaccines, oncolytic viruses, or TGFβ inhibitors do not show a benefit in the overall survival of patients. Thus, especially in PDAC and in respect to the immune system, there is an urgent need for sufficient preclinical systems that can mirror a human patient scenario. Therefore, we developed a human-based pipeline of whole explant tissue culture using PDAC to predict responses of the tumor to different types of treatments in a personalized manner. Material and Methods: Human cancer tissue is taken into culture after surgery for several days. We tested different timings and technical variations (e.g., thickness of explants, medium changing protocols) to find superior conditions for tissue viability. In culture, the explants can be treated with (pre-) clinical-grade drugs and subsequently processed for quality controls via evaluation of the tissue integrity (on H&E slides) and cytokine stability. Also, histologic analyzes (e.g., cancer cells, T cells, B cells, macrophages) as well as multiplex cytokine analyzes are carried out. This combined approach enables us to study the impact of various drugs on the tissue in terms of tumor cell death, changes in the infiltration and activation of lymphocytes and macrophage polarization, etc. Results In vivo features of the tissue and the matrix architecture as well as the cytokine signatures are well maintained in the explants. Our model is reproducible among different explants of the same tissue in terms of infiltrating cells and cytokine expression. In addition, we were able to achieve an overview of the cytokine signature of PDAC in patients and to distinguish between clusters of patients by identifying different immune landscapes, for example, immunologically hot and cold subtypes. Discussion: Our model is usable as a predictive system for the response of PDAC to different types of treatments and seems to be a reliable and sufficient preclinical extension alternative to mouse models, single-cell experiments, or organoid models. The whole context of the tissue is from human origin and we aim to expand our platform for multiscreening of drug responses for personalized decision-making. Furthermore, we described the tumor microenvironment in detail, unraveling the complex cytokine signature of PDAC, and subsequently identified different clusters of immune landscapes, which may be of prognostic value. Citation Format: Azaz Ahmed, Dyke Ferber, Meggy Suarez-Carmona, Bénédicte Lenoir, Rosa Klotz, Thilo Hackert, Nathalia Giese, Inka Zörnig, Dirk Jäger, Niels Halama. Establishment of a human PDAC explant culture model for treatment prediction and characterization of the tumor microenvironment [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr C02.

Recent studies have identified a putative cell of origin for cervical intraepithelial neoplasia (CIN) and cervical cancer at the squamocolumnar junction (SCJ) and suggest that these cells may not regenerate after excision (loop electrosurgical excision procedure). Our study addressed the impact of SCJ excision on the temporal dynamics, histologic and viral (human papillomavirus, HPV) characteristics of recurrent CIN. One hundred and thirty-one consecutive patients treated by excision and attending follow-up visits were enrolled. We compared recurrent and initial CIN with attention to excision margins, timing of recurrence, CIN grade, HPV types, p16 immunophenotype and SCJ immunophenotype. During the follow-up period (up to 4 years), 16 (12.2%) recurrences were identified. Four (25%) were identified at the first follow-up visit, closely resembled the initial CIN 2/3 in grade and HPV type and were typically SCJ marker positive [SCJ(+)], suggesting nonexcised (residual) disease. Twelve (75%) manifested after the first postoperative visit and all were in the ectocervix or in mature metaplastic epithelium. All of the 12 delayed recurrences were classified as CIN 1 and were SCJ (-). In total, 9 out of 11 SCJ (-) recurrences (82%) followed regressed spontaneously. Taken together, these results show that new lesions developing from any HPV infection are delayed and occur within the ectocervix or metaplastic epithelium. This markedly lower risk of CIN 2/3 after successful SCJ excision suggests that the removal of the SCJ could be a critical variable in reducing the risk of subsequent CIN 2/3 and cervical cancer.

Despite the immense research over the past decade in the cancer immunology field, which has led to several clinical trials and FDA and EMA approvals of biologicals for the reinvigoration of T-cell-mediated cancer cell killing in diverse tumor entities, the long-term survival of patients with advanced epithelial ovarian cancer is still devastating. These results therefore imply the need for a more intensive investigation of the tumor microenvironment in this cancer type in order to enhance disease outcome and improve the effectiveness of current immunotherapeutics. We herein show for the first time efficacy data of a novel treatment approach for the specific targeting of the stromal tumor compartment in a human tissue explant culture model of high-grade serous ovarian cancer. Antibody-mediated blockade of NIM15, a protein suspected to be predominantly expressed by tumor-associated macrophages and cancer-associated-fibroblasts in ovarian cancer, has the potential to polarize the immune landscape in a subset of patients from a stromal-dense and immunosuppressive one into a Th1-M1-supportive microenvironment, as measured by cytokine pattern analyses and semiautomated immune cell quantification. Abrogating the effects of secreted NIM15 unleashes in vitro proliferation of T-cell subsets and increases the production of cytokines and chemokines involved in innate and adaptive antitumor immune responses in our tissue culture explant model. In order to unravel the mechanistic relations behind the observed effects, we plan further experiments to prove whether these might be due to a disruption of the collagen-dense tumor stroma and a repolarization of the secretory profile of tumor-associated macrophages and fibroblasts. In summary, we hope to develop a pharmacologic tool that converts immune-depleted, “cold” cancer types into T-cell infiltrated ones and therewith provide a rationale for combination treatment approaches, like anti-PD1 blockade or adoptive cell transfer, to further ameliorate the so far poor response of metastasized, refractory ovarian cancer. Citation Format: Dyke Ferber, Meggy Suarez-Carmona, Frank Momburg, Marten Meyer, Rebecca Rothenheber, Bénédicte M.A. Lenoir, Sarah Schott, Inka Zoernig, Dirk Jäger, Niels Halama. NIM15 blockade – A new stroma-targeting approach for the treatment of epithelial ovarian cancer [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A069.

T-cell exclusion by tumors is one of the major obstacles for cancer immunotherapies. In colorectal cancer liver metastasis (CRC-LM) patients, effector T-cells are mainly found in the invasive margin and not in the tumor epithelium. Such T-cell exclusion might hinder an effective antitumor immune response and could account for therapy failures with immune checkpoint inhibitors, which is observed in the majority of CRC-LM patients. As T-cell infiltration and distribution are difficult to detect in patients, little is known about detailed immunotherapy effects on tumor-infiltrating lymphocytes (TIL). Therefore, we established a fully human tissue-based ex vivo cell migration analysis model to monitor T-cell infiltration and positioning in the authentic tumor microenvironment of CRC-LM patients. In brief, we isolated T-cells from fresh resected CRC-LM patient tissue samples, labeled the cells with a fluorescent dye and returned the labeled T-cells to the tissues, which were cultured for a certain time period. Besides autologous T-cells, several tissue samples were treated with non-autologous labeled T-cells isolated from a healthy donor. After tissue processing, immunostaining and cell quantification, we observed that remigration of the labeled autologous and donor T-cells into the tissues was significantly associated with numbers of endogenous TIL. The labeled autologous and donor T-cells showed a similar distribution pattern to endogenous TIL with highest densities in the invasive margin of patient tissues. No relevant changes in tumor cell numbers or apoptosis protein concentrations could be observed by both treatments. Furthermore, quantification of the chemokines CXCL9, CXCL10 and CCL5 showed significant associations with labeled autologous and donor T-cell infiltration. Interestingly, treatment with a PD1 inhibitor did not support infiltration of exogenous or endogenous T-cells into the tumor epithelium. Our findings highlight that infiltrating T-cells in CRC-LM are always positioned into the invasive margin independently of the T-cell´s origin. Especially microenvironmental factors such as CXCL9, CXCL10 and CCL5 seem to be involved in this process, preventing T-cell contact with the tumor epithelium, which could also not be abrogated by immune checkpoint inhibition. The similar infiltration and distribution pattern of T-cells in the ex vivo and in vivo settings highlights the functionality and reliability of the human tissue-based cell migration analysis model, emphasizing its use for studying therapy effects on TIL in CRC-LM patient tissues. Citation Format: Anna Berthel, Meggy Suarez-Carmona, Jakob N. Kather, Rodrigo Rojas-Moraleda, Pornpimol Chaorentong, Nektarios A. Valous, Fee Klupp, Martin Schneider, Alexis Ulrich, Markus Buechler, Inka Zoernig, Dirk Jaeger, Niels Halama. A fully human tissue-based ex vivo cell migration analysis model to study T-cell infiltration and distribution in colorectal cancer liver metastases [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A171.

Epithelial ovarian cancer (EOC) is an immunogenic tumor entity, as evidenced by multiple correlative studies indicating the impact of intraepithelial tumor-infiltrating T lymphocyte (TIL) density on patient outcome. Immunotherapy trials have generated modest results so far and chemotherapy remains standard of care. In this study, we focus on EOC metastases invading the omentum. Our aim is to characterize their immune landscape with the goal of identifying specific targetable characteristics of these metastases, which are the most prevalent and relate to high morbidity.We used a cohort of 120 ovarian cancer specimens for histologic analysis, cytokine, or metabolic profiling. Furthermore, we developed an EOC tissue explant culture model and treated whole-tissue explants with drugs before assessing immune cell density, distribution, and activation status. Finally, we cultured macrophages isolated from patient-derived ascites to study their response to various treatments.Samples were classified into omental metastases and primary tumors (based on the presence of fat on histologic sections). We observed that omental metastases are characterized by an inflamed microenvironment orchestrated by macrophages and are infiltrated by high amounts of TILs with low expression of activation markers, and a skewed localization around fat patches. These TILs express high amounts of the tumor-supporting CCL5 chemokine. Macrophages storing fatty acids in the form of big vacuoles were found in these fatty tumors as well. Targeting macrophages using the CCR5 inhibitor maraviroc in whole tissue explants effectively restored T-cell distribution across the tissue and slightly affected macrophage polarization specifically in fat-containing tumors. Inhibiting fatty acid import in macrophages more dramatically affected the cytokine landscape, also specifically in fat-containing tumors, and established a Th1-supporting environment permeable to T-cell expansion and activation. In brief, omental metastases are characterized by: (a) a smoldering inflammatory reaction and high macrophage density, (b) increased T-cell accumulation around fatty areas away from cancer cells, and (c) T-cell exhaustion accompanied by CCL5 expression. Treatment of EOC explants revealed that macrophages infiltrating omental metastases can be repolarized in situ, leading to TIL expansion and activation. Citation Format: Meggy Suarez-Carmona, Nektarios A. Valous, Pornpimol Charoentong, Jakob N. Kather, Mareike Hampel, Bénédicte M.A. Lenoir, Dyke Ferber, Sarah Schott, Sabine Kess, Inka Zoernig, Dirk Jaeger, Niels Halama. Omental fat in ovarian cancer induces metabolic and immune alterations [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A114.

Ovarian cancer metastasis occurs by direct multifocal seeding into the peritoneum as well as by migration through the lymphatic system. High-grade ovarian carcinoma patients often present with distant metastases. Significant risk factors for the development of those are stage, grade, and lymph node involvement. The increase of the number of lymphatic vessels seems to be implicated in ovarian tumor progression. While the tropism of ovarian cancer cells for fat is well described, the potential impact of an adipose-rich microenvironment on the dissemination of metastasis via lymphatic vessels has never been investigated. So far, in this study, we examined the effect of omental fat on lymphangiogenesis in ovarian carcinoma. For that we used a cohort of 80 ovarian cancer specimens. We observed a higher number of tumor-associated vessels and principally lymphatic vessels in ovarian cancer in contact with the omentum. These lymphatic vessels are predominantly localized along the fat tissue. A higher secretion of VEGF-C is observed in ovarian tissues containing fat compared to the ones without fat, giving a potential explanation to the observed increase of lymphatic vessels in fatty tissues. We also developed a healthy fat tissue explant culture model and treated whole tissue explants with ascites. Herein, we saw an increase of the number of adipose-derived stem cells (ADSCs). These ADSCs express lymphatic markers such as D2-40 and Lyve-1. We also observed an impact of fat supernatant on the proliferation, migration and tube formation of lymphatic endothelial cells in vitro. In conclusion, we can say that omental fat in ovarian cancer seems to have an impact on lymphangiogenesis. The close contact of ascites with fat tissue seems to lead to a differentiation of adipose-derived stem cells into lymphatic endothelial cells. Further investigations must be performed to understand the exact mechanisms underlying this phenomenon. Citation Format: Bénédicte M.A. Lenoir, Dyke Ferber, Victor Starrach, Meggy Suarez-Carmona, Sarah Schott, Inka Zoernig, Dirk Jäger, Niels Halama. Omental fat in ovarian cancer induces lymphangiogenesis [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A086.

The influence of the local immune response on the clinical course of colorectal cancer (CRC) has been analyzed extensively. Analyzing the invasive margin of human CRC liver metastases, we identified a protumoral mechanism of T-cell-derived CCL5 that leads to immune cell exploitation by tumor cells. Two distinct subsets of myeloid cells produce CXCL9/CXCL10, which induce an influx of T cells into the invasive margin. CCL5 is produced by these exhausted T cells and stimulates tumor cell proliferation and invasive behavior via CCR5 on tumor cells and macrophages. CCR5 inhibition in patient-derived functional in vitro organotypic culture models induced macrophage repolarization with anti-tumoral effects. These immunomodulatory and anti-tumoral effects of CCR5 blockade then could be confirmed in a phase I trial with a CCR5 antagonist in advanced refractory CRC patients with liver metastases. Amelioration of tumor-promoting inflammation on the tumor tissue level and objective tumor responses in advanced metastatic CRC patients were observed. Citation Format: Niels Halama, Inka Zoernig, Anna Berthel, Christoph Kahlert, Fee Klupp, Meggy Suarez-Carmona, Juergen Krauss, Karsten Brand, Felix Lasitschka, Tina Lerchl, Claudia Luckner-Minden, Alexis Ulrich, Juergen Weitz, Martin Schneider, Markus W. Buechler, Laurence Zitvogel, Thomas Herrmann, Axel Benner, Christina Kunz, Stephan Luecke, Christoph Springfeld, Christine Falk, Dirk Jaeger. Macrophage repolarization therapy in metastatic colorectal cancer: CCR5 inhibition [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B037.

Because of the particular anatomy of ovaries, which are in close contact with the adipocyte-rich omentum, ovarian cancer frequently presents itself with established metastasis-like disseminated tumor islets along the omentum. The tropism of ovarian cancer cells for fat is well described. Indeed, adipocyte-derived free fatty acids have been causatively linked to cancer cell proliferation and invasive properties. Obesity is additionally linked to increased risk of ovarian cancer onset and, in ovarian cancer patients, to worse outcome. However, there is to our knowledge no clear association between omentum-anchored dissemination and the anti-tumor immune response. Here we describe an unsuspected association between the presence peritoneal fat in ovarian tumors and massive tumor infiltration by T cells. Still, this massive T cell influx seems to fail in its anti-tumor activity since (1) tumor-infiltrating T cells seem to be hijacked away from tumor cells and accumulate around fatty areas and (2) tumor-infiltrating T cells display an exhausted phenotype. In this presentation, we also describe a new model of tissue culture of explants from primary human tumors that are treated with various drugs in an attempt to circumvent this fat-derived immune exhaustion and restore an efficient anti-tumor immune response. Citation Format: Meggy Suarez-Carmona, Anita Heinzelmann, Nektarios A. Valous, Mareike Hampel, Anna Berthel, Sarah Schott, Inka Zörnig, Dirk Jäger, Niels Halama. The fat in ovarian cancer: Immune-dependent tumor-promoting effects [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A102.