Convergence of Technology and Cancer Immunotherapy最新文献

{"title":"Abstract B032: PhIP-seq assessment of the serum antibody repertoire before and after immune-related adverse events in four melanoma patients treated with checkpoint blockade immunotherapy","authors":"Tim O’Donnell, M. Shan, E. Merritt, E. G. Gugel, Ana B. Blasquez, M. Meseck, P. Friedlander, A. Rubinsteyn, A. Horowitz, N. Bhardwaj, Uri Laserson","doi":"10.1158/2326-6074.CRICIMTEATIAACR18-B032","DOIUrl":"https://doi.org/10.1158/2326-6074.CRICIMTEATIAACR18-B032","url":null,"abstract":"Phage immunoprecipitation sequencing (PhIP-seq) is a technique to profile the epitope specificities of an antibody repertoire by phage display of a peptide library followed by immunoprecipitation and next-generation sequencing (1). We have developed phage libraries corresponding to all 36-mer peptides in the human proteome (approximately 413,000 peptides), as well as libraries of peptides found in viruses, bacteria, and toxins. Here, in a pilot study to understand if PhIP-seq might be used to identify predictive biomarkers for immune-related adverse events (irAE) in the context of checkpoint blockade immunotherapy, we applied the human proteome library to probe the self-directed IgG response in sera from four melanoma patients receiving checkpoint blockade who experienced irAE. In total, 16 serum samples acquired at the pre-treatment, post-treatment / pre-irAE, or post-irAE timepoints were assayed from these patients. We additionally analyzed samples from six melanoma patients who received vaccines targeting the MART-1 and NY-ESO-1 antigens. Using a stringent confidence threshold, we identified a median 31 self-directed antibody specificities (hits) at the pre-immunotherapy timepoint in these cancer patients and 41.5 hits post-therapy, compared to a median 6.5 hits in healthy donors. Patients receiving combination checkpoint blockade showed more hits than those treated with monotherapy. For a patient who received combination nivolumab and ipilimumab and developed a hepatic irAE, a cluster of 25 hits (of 161 total) was detected uniquely in a sample taken within two months subsequent to the adverse event. This cluster included a peptide from the C-Reactive Protein (CRP) gene and other genes expressed in the liver (EHBP1, VSTM2L), or across tissues (SAFB2), but also included genes with low expression in the liver (SPTBN4, DMBT1, IQGAP3, SPTBN4). In a patient who received ipilimumab and nivolumab and developed myalgia, hits against targets associated with autoimmune disease were found including NUMA1 (connective tissue autoimmunity), TRPM1 (melanoma-associated retinopathy), as well as three epitopes in the Mediator Of DNA Damage Checkpoint 1 (MDC1) gene. Finally, for three patients receiving a peptide vaccine targeting MART-1 and NY-ESO-1 with adjuvant poly-ICLC and montanide, we detected an IgG response against NY-ESO-1, but not MART-1, in each patient. No response to either protein was observed in three patients receiving a dendritic cell vaccine against the same antigens.Our small study suggests that PhIP-seq readily detects changes in the epitope specificities of the serum antibody repertoire in the course of immunotherapy. A key limitation of PhIP-seq is that the method can only detect antibodies with specificities for linear (as opposed to conformational) epitopes. Nevertheless, the assay’s low cost (approximately $30 per sample), small sample size requirement (1 µL serum), and ability to work with dried blood spot samples may make it an attrac","PeriodicalId":352838,"journal":{"name":"Convergence of Technology and Cancer Immunotherapy","volume":"100 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132244763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract B057: Enhancing immunotherapy for triple-negative and HER2+ breast cancer using EpCAM aptamer-siRNA mediated gene knockdown","authors":"Ying Zhang, J. Lieberman","doi":"10.1158/2326-6074.CRICIMTEATIAACR18-B057","DOIUrl":"https://doi.org/10.1158/2326-6074.CRICIMTEATIAACR18-B057","url":null,"abstract":"Triple-negative (TNBC) and HER2+ breast cancers (BCs) are especially aggressive tumors, which are prone to relapse and metastasize post chemo- or targeted therapy. Immunotherapy provides a promising, but unproven, alternative approach for treating poor-prognosis BCs. BCs have relatively low nonsynonymous mutation rates, suggesting that many BCs will respond poorly to immunotherapy. Novel strategies to increase BC cell immunogenicity and improve tumor-antigen specific T-cell responses are needed to enhance the efficacy of BC immune therapy. We aim to enhance the immunogenicity of breast tumor by taking advantage of the unique strength of EpCAM-aptamer conjugated small interfering RNAs (AsiCs), which can knock down gene expression selectively in EpCAM+ BC cells, to make aggressive BCs visible to T-cells and improve T-cell tumor recruitment and function. EpCAM is a tumor-specific antigen expressed at several logs higher levels on all epithelial cancers and cancer stem cells relative to normal epithelia. The EpCAM aptamer our lab developed binds with high affinity to both mouse and human EpCAM. Using this platform, we investigated the use of EpCAM-AsiCs for BC immune modulation by targeting genes controlling different functional processes: 1) knocking down the nonsense-mediated mRNA decay (NMD) gene UPF2, to elicit tumor neoantigen expression to improve BC tumor recognition by the immune system; 2) knocking down CD47 to promote phagocytosis of cancer cells and enhance cross-presentation of tumor antigens; 3) knocking down DNA repair enzyme PARP1 to produce more DNA damage and consequent genetic mutations, thereby introducing tumor-specific neoantigens to the immune system; 4) knocking down PLK1 which is essential for cell mitosis, and MCL1, which is a critical survival factor in TNBC, to directly kill tumor cells. The increased tumor cell death induced by PLK1 and MCL1 knockdown could potentially promote tumor antigen cross-presentation to CD8+ T-cells. Our data indicate that each of these AsiCs potently silences gene expression within mouse or human BC cell lines in vitro, and efficiently reduce target gene expression in EpCAM+ tumor cells in vivo. When treating mice bearing 4T1E (4T1 cell line with high EpCAM expression) tumors, EpCAM-AsiCs targeting UPF2, CD47, PARP1, PLK1 and MCL1 each significantly suppressed 4T1E tumor growth, increased CD8+ T-cell tumor infiltration, CD8+ T-cell/regulatory T-cells (Treg) ratio, the effector functions and degranulation capacity of CD8+ TILs compared to those of the control group. The capacity of these CD8+ TILs to directly kill tumor cells was also improved. Tumor-associated macrophages (TAMs) from CD47-AsiC treated tumors showed improved phagocytic capacity as determined by in vitro and in vivo phagocytosis assays. CD47-AsiC also increased the ratio of M1 (tumor suppressive) to M2 (tumor promoting) TAMs. Dendritic cells (DCs) from CD47-AsiC treated tumors show enhanced CD40 and CD86 expression, suggesting an i","PeriodicalId":352838,"journal":{"name":"Convergence of Technology and Cancer Immunotherapy","volume":"7 6","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132285645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract B059: Synergistic activation of antitumor immunity by an oncolytic virus VG161 armed with multiple immune-stimulating genes","authors":"R. Zhao, Jun Ding, Dmitry Choujenko, Y. Murad, E. Lee, Guoyu Liu, L. Bu, W. Jia","doi":"10.1158/2326-6074.CRICIMTEATIAACR18-B059","DOIUrl":"https://doi.org/10.1158/2326-6074.CRICIMTEATIAACR18-B059","url":null,"abstract":"Oncolytic viruses (OVs) are among the most powerful approaches in cancer immunotherapy. OVs not only cause cancer cell lysis but more importantly, their infection in tumors induces anti-tumor immune response from the host, resulting in lasting anti-tumor immunity. It has been recognized that anti-tumor immune response requires multiple immune regulatory factors that act synergistically and tumor microenvironment is critical for tumor to grow. Herpes simplex virus type-1 (HSV-1) has been approved by FDA as an oncolytic viral drug to treat melanoma. One advantage of HSV-1 is its large genomic capacity for carrying multiple exogenous genes.A HSV-1 oncolytic viral vector (VG161) was constructed to simultaneously express IL12, IL15 with its receptor alpha unit and a PDL-1 blocking peptide. Antitumor activity of VG161 was tested in both immune competent mice (CT26 and A20 tumor models) and nude mice for human tumor models (LNCaP and U87). Since CT26 and A20 are poorly permissive for HSV-1 replication, the mouse tumor models were able to demonstrate the antitumor immune response induced by VG161 while oncolytic activity of VG161 was demonstrated in LNCaP and U87 models since the immune system is compromised in those models.VG161 completely inhibited tumors in all the models tested and the animals survived tumor-free for many months till sacrificed. VG161 induced tumor oncolysis in both LNCaP and U87 tumors. In the CT26 model, animals were protected from the second challenging with CT26 cells following previous virally induced tumor regression. Furthermore, in a A20 double tumor model, intratumoral injection into the tumor on one side caused tumor regression on both sides. Transcriptome analysis showed significant change in tumor microenvironment. Finally, tumor specific memory T-cells were evident in the treated animals. The anti-tumor immune response by VG161 was significantly stronger than similar viruses that did not express any immune stimulating gene or only express GM-CSF. These results showed that intratumorally expressed multiple immune regulatory factors by an oncolytic virus may significantly change the tumor immune microenvironment to enhance efficacy of the oncolytic virus. Citation Format: Ronghua Zhao, Jun Ding, Dmitry Choujenko, Yanal Murad, Erica Lee, Guoyu Liu, Luke Bu, William Jia. Synergistic activation of antitumor immunity by an oncolytic virus VG161 armed with multiple immune-stimulating genes [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 B059.","PeriodicalId":352838,"journal":{"name":"Convergence of Technology and Cancer Immunotherapy","volume":"25 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133811025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract B020: T-cell recognition of large T and small T antigen in Merkel cell polyomavirus-associated cancer","authors":"U. Hansen, R. Lyngaa, P. Straten, J. Becker, C. Church, P. Nghiem, S. Hadrup","doi":"10.1158/2326-6074.CRICIMTEATIAACR18-B020","DOIUrl":"https://doi.org/10.1158/2326-6074.CRICIMTEATIAACR18-B020","url":null,"abstract":"Merkel cell carcinoma (MCC) is an aggressive human skin cancer mainly induced by Merkel cell polyomavirus (MCPyV). While the virus is common in humans, the unlikely event of oncogenic transformation occurs only rarely, and development of MCC is furthermore primarily seen in immunosuppressed and elderly. Indicating, that despite oncogenic potential further lack of immunosurveillance is necessary for cancer development. Two mutation events, often inflicted by UV light, allow the clonal integration of the viral genome into the host genome and the translation of the two viral oncogenes large T (LTA) and small T antigen (STA). The importance of immune recognition for clearing disease was segmented by the encouraging results using anti-PD1 for treatment of metastatic MCC. Recently, the first PD-1 checkpoint inhibitor (avelumab) became FDA approved. To further understand the mechanism of action, and to direct T-cell responsiveness specifically to MCC, there is a great interest to identify T-cell epitopes in MCPyV. To date, several T-cell epitopes derived the MCPyV-derived proteins LTA, STA and viral capsid protein1 (VP1) have been described. However, only restricted to a limited number of HLA types (HLA-A01, -A02, -A03, -A11, -A24 and B07). Here we aim to expand the knowledge about T-cell epitopes by including a broader range of HLA restrictions (HLA-B08, -B35 and -B44). Potential T-cell epitopes were selected by in-silico prediction. Given a total of 148 peptides across the nine MHC class I. Peripheral blood mononuclear cells (PBMC) from 49 patients were analyzed using a platform consisting of a magnetic-based enrichment of MHC multimer binding cells, which allowed detection of low frequency T-cell clones after 2-3 weeks of culturing. Followed by detection of T-cell reactivity against the MCPyV-derived epitopes using combinatorial color encoding of MHC multimer. Using this strategy, we identified 60 MCPyV-directed T-cell responses against 34 different peptides in PBMC from 31 of the patients. Furthermore, three patients’ tumor-infiltrating lymphocytes (TIL) were analyzed directly ex vivo for detection of T-cell reactivity against the MCPyV-derived peptides. We identified four MCPyV-directed T-cell responses against four different peptides. Importantly, epitope targets embedded in the LTA and STA proteins were solely observed in the patient samples while T-cell recognition of the capsid protein VP1 was observed in both patients and healthy donors. For selected LTA/STA-derived epitopes processing and presentation were demonstrated in MCC tumor cell lines, as well as the functional capacity of LTA/STA responsive CD8 T-cells. The identification of novel LTA/STA-derived epitopes will facilitate the use of targeted T-cell therapy to enhanced MCC recognition and clearance in combination with checkpoint inhibition. Such strategies should be tailored according to the patient’s HLA type, and hence expanding the epitope repertoire with additional HLA restrictions","PeriodicalId":352838,"journal":{"name":"Convergence of Technology and Cancer Immunotherapy","volume":"77 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133304779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract B034: A novel immunomodulatory strategy of targeting glyco-immune checkpoints with EAGLE technology","authors":"Li Peng","doi":"10.1158/2326-6074.CRICIMTEATIAACR18-B034","DOIUrl":"https://doi.org/10.1158/2326-6074.CRICIMTEATIAACR18-B034","url":null,"abstract":"Cancer therapy has been revolutionized by inhibiting immune checkpoints to harness the power of the immune system in fighting cancer. However, the majority of patients are resistant to the current immuno-oncology drugs. There is a strong need to identify novel mechanisms of cancer immune evasion and explore novel therapeutic modalities. Glyco-immune checkpoint axis plays a critical role in modulating innate and adaptive immune responses against cancer. However, this pathway is underexplored for therapeutic interventions of cancer, because the complexity and heterogeneity of glycan-ligands on tumor cells pose grand challenges for conventional therapeutic modalities. Here we described a novel multifunctional antibody-like therapeutic modality, named EAGLE (Enzyme-Antibody Glyco-Ligand Editing), which can overcome the heterogeneity and complexity problems and specifically edit tumor-specific glycans. We evaluated the efficacy of an EAGLE molecule and studied its mechanism of actions in a breast cancer EMT6 syngeneic tumor model. Systematic delivery of the EAGLE molecule decreased the expression levels of immunosuppressive glycan-ligands on tumor cell surfaces, and increased T-cell infiltration and activation in the syngeneic tumor models. EAGLE treatment led to 50% complete regressions of established tumors as a monotherapy and 100% cures in combination with an anti-PD1 mAb. Furthermore, cured mice from EAGLE treatment completely rejected the rechallenge of tumor cells, suggesting that EAGLE induced anti-tumor immunologic memory. In summary, the novel therapeutic modality, EAGLE, blocked the glyco-immune checkpoint pathway in the tumor microenvironment and potentiated innate and adaptive antitumor immunity, which offers a novel immunomodulatory strategy to treat cancer. Citation Format: Li Peng. A novel immunomodulatory strategy of targeting glyco-immune checkpoints with EAGLE technology [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 B034.","PeriodicalId":352838,"journal":{"name":"Convergence of Technology and Cancer Immunotherapy","volume":"2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124571223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract B046: Immune repertoire sequencing enables complete B-cell and T-cell clonality determination and minimal residual disease assessment","authors":"Chen Song, Luo Sun, Pingfang Liu, B. Langhorst, A. Barry, T. Davis, E. Dimalanta","doi":"10.1158/2326-6074.CRICIMTEATIAACR18-B046","DOIUrl":"https://doi.org/10.1158/2326-6074.CRICIMTEATIAACR18-B046","url":null,"abstract":"The study of complex immunologic diseases and tumor microenvironment has progressed through recent developments that enable the sequencing of the immune repertoire. Using this approach, the interrogation of disease progression is facilitated through analysis of millions of V(D)J combinations from both B cell antibodies (Igs) and T-cell receptors (TCRs). One major challenge of immune repertoire sequencing is to capture the structural and sequence complexities of antibody and TCR genes. We have developed and optimized a method for accurate sequencing of full-length immune gene repertoires of B-cells and T-cells. RNA extracted from tissue and PBMCs were used to generate immune sequencing libraries. Using a unique molecule index (UMI) to discretely barcode each mRNA molecule, PCR copies of each mRNA fragment can be collapsed into a single consensus sequence. The B cell genes were enriched during library preparation by IGH, IGK and IGL primes, including isotype-specific primers (IgA, IgD, IgE, IgG and IgM). The T-cell genes were enriched by TCRα and TCRβ specific primers. To investigate the applicability of minimal residual disease assessment, we obtained Jurkat RNA, a homogenous population of leukemic Jurkat T-cells and spiked it into a PBMC RNA sample at varying proportions of Jurkat RNA (10%, 1%, 0.1%, 0.01% and 0.001%). The RNA mixtures were made into TCR libraries, sequenced on both Illumina MiSeq and Oxford Nanopore MinION, and analyzed to assess the TCR repertoire. Utilization of UMIs enabled absolute quantification of the B cell antibody/TCR clones and accurate ranking of their abundance. For B cell repertoire sequencing, the use of isotype-specific primers enabled measurement of the heavy chain isotype proportions within the samples. Full-length heavy chain antibody analysis enabled measurement of the mutation level of each antibody sequence, providing information on the overall maturity and mutational profile of the sample repertoire. For TCR repertoire sequencing, distinct and shared clonal sequences were quantitatively detected in PBMC samples. The method also accurately and sensitively detected the control TCR clone spiked into both Illumina and Oxford Nanopore libraries at levels appropriate for minimal residual disease assessment.This immune repertoire sequencing approach allows accurate clonal determination for both Igs and TCRs. This technique is applicable for a variety of applications including design of antibody chains for in vitro synthesis, investigation of T-cell infiltration of tumor microenvironments, and monitoring of minimal residual disease. Citation Format: Chen Song, Luo Sun, Pingfang Liu, Bradley Langhorst, Andrew Barry, Theodore B. Davis, Eileen T. Dimalanta. Immune repertoire sequencing enables complete B-cell and T-cell clonality determination and minimal residual disease assessment [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Surv","PeriodicalId":352838,"journal":{"name":"Convergence of Technology and Cancer Immunotherapy","volume":"21 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131824663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract B050: Identification of PD-1T TILs and CXCL13 as determinants for response to anti-PD-1 treatment using human tumor explants","authors":"D. Thommen, V. Koelzer, P. Herzig, Marjolein de Bruijn, P. Voabil, M. Braber, Karlijn Hummelink, K. Monkhorst, K. Mertz, A. Zippelius, J. Haanen, T. Schumacher","doi":"10.1158/2326-6074.CRICIMTEATIAACR18-B050","DOIUrl":"https://doi.org/10.1158/2326-6074.CRICIMTEATIAACR18-B050","url":null,"abstract":"Reinvigoration of tumor-specific T-cells by cancer immunotherapies, in particular PD-1/PD-L1 blocking agents, has greatly improved clinical outcome in multiple cancer types. Nevertheless, durable clinical benefit is currently limited to a small number of patients. To achieve a better understanding of the immunologic determinants of response to anti-PD-1 therapy, we assessed transcriptional and functional profiles of tumor-infiltrating lymphocyte (TIL) subsets from non-small cell lung cancer specimens. Thereby, we identified a transcriptionally distinct CD8 TIL pool with enriched capacity for tumor recognition. This TIL pool, termed PD-1T TILs, is characterized by bright PD-1 expression and constitutive CXCL13 secretion, which can mediate immune cell recruitment to tertiary lymphoid structures. Notably, the presence of PD-1T TILs correlates with response and survival in a small cohort of lung cancer patients treated with PD-1 blockade. To assess the role of PD-1T TILs and CXCL13 for response to PD-1 blockade in other cancer types, we developed a platform using human tumor explants to visualize immunologic responses to anti-PD-1 on a patient-specific level. Analysis of the cellular and soluble tumor microenvironment composition as well as of treatment-induced changes in tumor-infiltrating immune cells revealed immunologic responses to anti-PD-1 in 5 different cancer types. Of note, responding tumors in different tumor types were characterized by a clear enrichment in both PD-1T TILs and CXCL13 production. Collectively, our data reveal a distinct state of PD-1 bright lymphocytes that are enriched for tumor-reactivity in human cancer, making them an attractive proxy for the antitumor potential of the intratumoral T-cell pool. Furthermore, we established technology using human tumor explants to measure the immunologic response to T-cell checkpoint inhibition on a personalized basis. Finally, with this approach we identified PD-1T TILs and CXCL13 as determinants for response to anti-PD-1 in multiple cancer types, opening potential new avenues for therapeutic intervention and improved patient selection. Citation Format: Daniela S. Thommen, Viktor H. Koelzer, Petra Herzig, Marjolein de Bruijn, Paula Voabil, Marlous van den Braber, Karlijn Hummelink, Kim Monkhorst, Kirsten D. Mertz, Alfred Zippelius, John B.A.G. Haanen, Ton N.M. Schumacher. Identification of PD-1T TILs and CXCL13 as determinants for response to anti-PD-1 treatment using human tumor explants [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 B050.","PeriodicalId":352838,"journal":{"name":"Convergence of Technology and Cancer Immunotherapy","volume":"2012 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129694547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}