Abstract 620: Tumor microenvironment heterogeneity is not identified across multiple histologically similar tumors from the same patient
Authors: Morrison Carl D. , Conroy Jeffrey , Glenn Sean , Burgher Blake , Pabla Sarabjot , Qin Maochun , Papanicolau-Sengos Antonios , Andreas Jon , Giamo Vincent , Nesline Mary , Gandhi Shipra , Pandey Manu , Ammannagari Nischala , Odunsi Kunle , Ernstoff Marc , Gardner Mark 
Published: July 2017

Introduction: Tumor heterogeneity has been well documented for mutational analysis in virtually all types of tumors and is accepted as a true finding. Heterogeneity of the tumor microenvironment (TME) in the context of response to checkpoint inhibitors has not been well studied; the belief is that variation will be identified across multiple tumors from the same patient. The expectation is that multiple tumors from a single patient would demonstrate extensive TME heterogeneity driven by the neoplasm.

Methods: We validated and utilized a targeted RNA-seq immune panel of &gt;350 genes to interrogate the TME of 49 different tumors from 17 unique patients. These samples for one patient represented primary and metastatic tumors that were separated by multiple years. Prior to this study we built a reference database of RNA-seq immune results for this panel of 167 samples. An in-depth analysis of genes associated with checkpoint inhibition (CPI) and tumor infiltrating lymphocytes (TILs) were the focus of the comparative analysis. Unsupervised analysis and gene rank by RNA-seq were the primary modes of comparison.

Results: For more than one-half of these patients the different tumors for a single patient separated by multiple years more closely resembled the other tumors from that patient than the reference population by unsupervised clustering. When ranked by LOW, MODERATE, or HIGH expression of genes associated with TILs or CPI the results for the majority of patients were highly concordant: LOW TILs / LOW CPI associated gene expression.

Conclusion: Our results support a paradigm shift in the influence of the host on TME heterogeneity with evidence that the host and not the neoplastic cells are the primary determining factor. TME heterogeneity is not identified across multiple tumors of the same histology collected from different sites across time points from the same patient. This study does not evaluate multiple primary tumors from the same patient, but is an additional study we have planned.

Subject IDM-PathT-PathPMRSpecimen YearTILs ScoreTILs InterpretationCPI ScoreCPI Interpretation1MelanomaLymph node NOSMetastatic200945LOW13LOW1MelanomaSubcutaneous tissue NOSMetastatic20108LOW2LOW2Bladder cancerUrinary bladder NOSPrimary201237LOW16LOW2Bladder cancerUrinary bladder NOSPrimary201310LOW11LOW2Bladder cancerSoft TissueMetastatic201414LOW23LOW3MelanomaBrain NOSMetastatic201058MODERATE37LOW3MelanomaDuodenum NOSMetastatic201251MODERATE41LOW4MelanomaSoft Tissue NOSMetastatic200598HIGH88HIGH4MelanomaSoft Tissue NOSMetastatic200522LOW3LOW5MelanomaMesentery NOSMetastatic201245LOW35LOW5MelanomaPeritoneum NOSMetastatic201487HIGH86HIGH6Bladder cancerUrinary bladder NOSPrimary20095LOW4LOW6Bladder cancerLung NOSMetastatic201243LOW41LOW7MelanomaSkin of Trunk NOSMetastatic20114LOW4LOW7MelanomaChest wall NOSMetastatic20122LOW1LOW7MelanomaSoft TissueMetastatic201225LOW25LOW8Lung adenocarcinomaLung right upper lobe of, NOSPrimary200999HIGH88HIGH8Lung adenocarcinomaLung right upper lobe of, NOSPrimary201688HIGH80HIGH9MelanomaLymph node NOSMetastatic20092LOW5LOW9MelanomaSmall intestine NOSMetastatic20110LOW1LOW10MelanomaSkin of Lower Extremity NOSMetastatic201216LOW8LOW10MelanomaLymph node NOSMetastatic201243LOW31LOW10MelanomaSkin of Lower Leg NOSMetastatic20134LOW13LOW11MelanomaLung left lower lobe of, NOSMetastatic201214LOW5LOW11MelanomaSkin of Scalp NOSPrimary201022LOW20LOW12Lung adenocarcinomaLung NOSPrimary201089HIGH77HIGH12Lung adenocarcinomaBrain NOSMetastatic201441LOW13LOW13MelanomaLiver NOSMetastatic201166MODERATE51MODERATE13MelanomaLymph node NOSMetastatic201147LOW13LOW14Renal cell carcinomaLung right lower lobe of, NOSMetastatic201395HIGH87HIGH14Renal cell carcinomaAdrenal gland NOSMetastatic201465MODERATE71MODERATE15Lung adenocarcinomaLung right middle lobe of, NOSPrimary201488HIGH75HIGH15Lung adenocarcinomaBrain NOSMetastatic201526LOW1LOW16MelanomaTonsil NOSMetastatic201462MODERATE53MODERATE16MelanomaSoft TissueMetastatic201513LOW1LOW17MelanomaDura Mater NOSMetastatic201553MODERATE16LOW17MelanomaLymph node NOSMetastatic201599HIGH88HIGH

Citation Format: Carl D. Morrison, Jeffrey Conroy, Sean Glenn, Blake Burgher, Sarabjot Pabla, Maochun Qin, Antonios Papanicolau-Sengos, Jon Andreas, Vincent Giamo, Mary Nesline, Shipra Gandhi, Manu Pandey, Nischala Ammannagari, Kunle Odunsi, Marc Ernstoff, Mark Gardner. Tumor microenvironment heterogeneity is not identified across multiple histologically similar tumors from the same patient [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 620. doi:10.1158/1538-7445.AM2017-620