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32Nd Annual Meeting and Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2017): Part One National Harbor, MD, USA

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32Nd Annual Meeting and Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2017): Part One National Harbor, MD, USA J Immunother Cancer: first published as 10.1186/s40425-017-0289-3 on 7 November 2017. Downloaded from Journal for ImmunoTherapy of Cancer 2017, 5(Suppl 2):86 DOI 10.1186/s40425-017-0289-3 MEETINGABSTRACTS Open Access 32nd Annual Meeting and Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2017): Part One National Harbor, MD, USA. 8-12 November 2017 Published: 7 November 2017 About this supplement These abstracts have been published as part of Journal for ImmunoTherapy of Cancer Volume 5 Supplement 2, 2017. The full contents of the supplement are available online at https://jitc.biomedcentral.com/articles/supplements/volume-5-supplement-2. Please note that this is part1of2. Oral presentations tochemistry, and tumor transcriptomic profiling. To assess differential neoantigen immunogenicity, we performed neoantigen fitness mod- O1 eling integrating clonal genealogy, epitope homology, and T cell Identification of unique neoantigen qualities in long-term receptor affinity. To examine in vivo T cell-neoantigen reactivity, we pancreatic cancer survivors used functional assays in a subset of very long-term PDAC survivors Vinod Balachandran1, Marta Luksza2, Julia N. Zhao1, Vladimir Makarov1, (n=7, median OS 10.5 years). John Alec Moral1, Romain Remark3, Brian Herbst1, Gokce Askan1, Results Umeshkumar Bhanot1, Yasin Senbabaoglu1, Danny Wells4, Charles Ian We found that tumors of long-term survivors displayed 12-fold Ormsby Cary4, Olivera Grbovic-Huezo1, Marc Attiyeh1, Benjamin Medina1, greater cytolytic CD3+CD8+Granzyme-B+ cells, with >94% of intratu- Jennifer Zhang1, Jennifer Loo1, Joseph Saglimbeni1, Mohsen Abu-Akeel1, moral T cell clones unique to tumors and not shared with adjacent Roberta Zappasodi1, Nadeem Riaz1, Martin Smoragiewicz5, Olca Basturk1, normal pancreatic tissue, suggesting intratumoral antigen recogni- Mithat Gönen1, Arnold J. Levine2, Peter J. Allen1, Douglas T. Fearon6, tion. Tumors of long-term survivors exhibited greater TCR repertoire Miriam Merad3, Sacha Gnjatic3, Christine Iacobuzio-Donahue1, Jedd diversity compared to tumors of short-term survivors, implying differ- Wolchok1, Ronald DeMatteo7, Benjamin Greenbaum8, Taha Merghoub1, ential antigenic targets. In examining neoantigens as potential T cell Steven Leach1 targets, we found that patients with both the highest predicted 1Memorial Sloan Kettering Cancer Center, New York, NY, USA; 2Institute neoantigen number and the greatest CD3+CD8+ infiltrates together for Advanced Study, Princeton, NJ, USA; 3Icahn School of Medicine at but not either parameter alone, exhibited the longest survival http://jitc.bmj.com/ Mount Sinai, New York, NY, USA; 4Parker Institute for Cancer (median OS not reached vs. 0.8y, P=0.004). In investigating possible Immunotherapy, San Francisco, CA, USA; 5University of Cambridge, unique neoantigen qualities in long-term survivors, a neoantigen Cambridge, UK; 6Cold Spring Harbor, Cold Spring Harbor, NY, USA; quality model conferring greater immunogenicity to dominant 7University of Pennsylvania, Philadelphia, PA, USA; 8Tisch Cancer neoantigens with homology to microbial epitopes identified long- Institute, New York, NY, USA term survivors independent of confounding variables and chemo- Correspondence: Vinod Balachandran ([email protected]) therapy (Neoantigen QualityHi vs. Low - median OS 8.6y vs. 0.8y; Journal for ImmunoTherapy of Cancer 2017, 5(Suppl 2):O1 P=0.002) whereas a model ascribing greater immunogenicity to in- creasing neoantigen number did not (Neoantigen QuantityHi vs. Low - on September 29, 2021 by guest. Protected copyright. Background median OS 0.8y vs. 1y; P=0.3) (Fig. 1). Similarly, neoantigen quality, Pancreatic adenocarcinoma (PDAC) is a lethal cancer with <7% of pa- but not quantity, was independently prognostic of survival in a lar- tients surviving past 5 years. T cell immunity has been linked to the ger, independent cohort unselected by survival (n =166; Neoantigen exceptional outcome of the rare long-term survivors but the antigens QualityHi vs. Low - median OS 30m vs. 14m; P<0.0001) (Fig. 1). Finally, we are unknown. detected lasting circulating T cell reactivity to both high quality neoanti- Methods gens and cross-reactive antigens in PDAC survivors, including identical To identify T cell antigens in long-term PDAC survivors, we assem- intratumoral clones with specificity to both (n=5 of 7 patients tested). bled the largest cohorts of stage-matched short [n=68, median over- Conclusions all survival (OS) 0.8y] and long-term PDAC survivors (n=82, median Our results identify neoantigens with unique qualities as T cell targets OS 6y). To enable antigen discovery, we performed a combined in PDAC. More broadly, we identify neoantigen quality as a biomarker analysis of whole exome sequencing, neoantigen prediction, T cell for immunogenic tumors that may facilitate rational application of receptor (TCR) Vβ-chain sequencing, 9-color multiplexed immunohis- immunotherapies. © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. J Immunother Cancer: first published as 10.1186/s40425-017-0289-3 on 7 November 2017. Downloaded from Journal for ImmunoTherapy of Cancer 2017, 5(Suppl 2):86 Page 2 of 244 O3 Combining immunophenomics with a gene expression panel for improved prostate cancer recurrence prediction Nathalie Harder1, Harald Hessel2, Maria Athelogou1, Alexander Buchner2, Christian Stief2, Thomas Kirchner2, Günter Schmidt1, Ralf Huss1 1Definiens AG, Munich, Germany; 2Ludwig-Maximilians-University Munich, Munich, Germany Correspondence: Nathalie Harder ([email protected]) Journal for ImmunoTherapy of Cancer 2017, 5(Suppl 2):O3 Background Multi-omics data provide rich information on different levels such as genome, transcriptome, function or phenotype. Integrating such com- prehensive measures offers great potential for identifying improved prognostic and predictive signatures in the context of precision medi- cine. Here we combine gene expression data with phenomic readouts Fig. 1 (abstract O1). Neoantigen quality is prognostic of pancreatic extracted from immunohistochemically stained sections of resected cancer survival prostate cancer (PCa) tissue. By integrating both data sets we identify multi-variate signatures with high prognostic value regarding prostate cancer recurrence after radical prostatectomy. Methods Data was collected from a cohort of 23 PCa patients (Gleason-score 6-9, O2 pT2, age<=75y). Consecutive FFPE tissue sections were dual-stained for Predictive biomarkers for response to anti-CTLA-4 and anti-PD-1 immune-related (CD3/CD8, CD68/CD163) and structural (CD34, CK18/ immunotherapy in melanoma patients p63) components. Using Tissue Phenomics, we extracted image-based Priyanka Subrahmanyam1, Zhiwan Dong2, Daniel Gusenleitner2, Anita features, e.g., densities, ratios, and distances of positive cells across dif- Giobbie-Hurder2, Mariano Severgnini2, Jun Zhou2, Michael Manos2, ferently stained sections after co-registration in specific regions-of- Holden Maecker1, F. Stephen Hodi2 interest (tumor, TME, stroma) [1]. Gene data (NanoString Technologies, 1Stanford University, Stanford, CA, USA; 2Dana-Farber Cancer Institute Seattle, nCounter PanCancer Immune Profiling Panel) was collected and Harvard Medical School, Boston, MA, USA from sections containing tumor only and normalized w.r.t. housekeep- Correspondence: Priyanka Subrahmanyam ([email protected]) ing genes. We separately selected subsets of image-based and Journal for ImmunoTherapy of Cancer 2017, 5(Suppl 2):O2 gene-based features by optimizing a cutoff regarding the uni-variate stratification performance (log-rank test, accuracy) on random data sub- Background sets using bootstrapping. Features from both sets were combined by Immune checkpoint blockade has greatly improved clinical outcomes Classification and Regression Trees (depth=2) and the best performing in melanoma patients. However, there is an urgent need for predict- combinations were identified using cross validation. Clinical parameters ive biomarkers to determine who will likely benefit most from which (age, Gleason-score, PSA blood value) provided no prognostic value as therapy. To date, most biomarkers of response have been identified shown by Cox regression analysis. in the tumors themselves. Biomarkers that could be assessed from Results peripheral blood would be even more desirable, because of ease of Several tree models showed improved cross-validated stratification access and reproducibility of sampling. performance compared to all uni-variate stratifications using either Methods feature set (Fig. 1). We found that (I) a low expression of C4B gene in http://jitc.bmj.com/ We used mass cytometry (CyTOF), which is a technique similar to combination with a low ratio of CD8(+) in stroma to CD3(+)CD8(-) in flow cytometry, but uses metal-ion tagged antibodies for high- tumor (pcrossVal<0.05), and (II) a high expression of CD46 gene in dimensional immune profiling. We performed CyTOF on pre- combination with a
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