Immune gene expression, survival outcome and response to PD-1/PD-L1 blockade: a TCGA pan-cancer analysis.

Authors

null

Elia Seguí

Hospital Clínic de Barcelona. Universitat de Barcelona, Barcelona, Spain

Elia Seguí , Laia Paré , Barbara Adamo , Estela Pineda , Mercedes Marín-Aguilera , Òscar Reig , Javier Garcia Corbacho , Montserrat Munoz , Manel Juan , Victoria Sanchez , Margarita Viladot , Carme Font , Daniel Benitez , Cristina Nadal , Nuria Vinolas , Núria de la Iglesia , Begona Mellado , Juan Maurel , Noemi Reguart , Aleix Prat

Organizations

Hospital Clínic de Barcelona. Universitat de Barcelona, Barcelona, Spain, Translational Genomics and Targeted Therapeutics in Solid Tumors Lab (IDIBAPS), Medical Oncology. Hospital Clínic Barcelona, Barcelona, Spain, Medical Oncology, Hospital Clínic de Barcelona, Barcelona, Spain, Medical Oncology, Hospital Clínic Barcelona, Barcelona, Spain, Centre Diagnostic Biomèdic (CDM), Barcelona, Spain, Hospital Clínic de Barcelona, Barcelona, Spain

Research Funding

Other

Background: Immune infiltration predicts survival in particular cancer-types. However, differences in immune profiling and associations with patient outcomes among multiple cancer-types have not been fully explored. Methods: Clinical and RNA-seq data from 9,761 tumors representing 30 cancer-types were obtained from TCGA project. The expression of 35 immune-related gene signatures tracking various cell-types was evaluated, including PD1, CTLA4, CD8A and CD4 genes. Association of each signature with overall survival (OS) was evaluated using Cox models. Correlations between each signature and the overall response rates (ORR) following anti-PD1/PDL1 monotherapy in each cancer-type (as reported in the literature) were evaluated across 16 cancer-types. Results: In the combined dataset, 15 out of 35 signatures (43%) mostly tracking cytotoxic T-cell response (e.g. CD8-T-cell, PD1 and CD8A) were highly correlated (mean coefficient [cc] = 0.69). The top 5 cancer-types with the highest percentages of samples expressing cytotoxic T-cell response signatures were lung adenocarcinoma (LUAD), thymoma, testicular cancer, melanoma and basal-like breast cancer. The top 5 cancer-types with the lowest percentages were chromophobe renal cell, pheochromocytoma/paraganglioma, prostate cancer, adrenocortical cancer and uveal melanoma. In terms of OS, expression of T-cell response signatures (as a continuous variable) was consistently associated with better outcomes in melanoma, endometrial adenocarcinoma, head and neck carcinoma, hepatocarcinoma, bladder cancer and LUAD, and with worse outcomes in low grade glioma, uveal melanoma, glioblastoma and clear cell renal carcinoma. Finally, high expression of CD8A gene, CD8-T-cell signature and PD1 gene was found highly correlated (cc = 0.68, 0.62 and 0.77, P< 0.001) with ORR following anti-PD1/PDL1 therapy. Conclusions: Significant differences in the expression of immune signatures exist within and across cancer-types. Whereas the association of cytotoxic T-cell response with OS might be dependent on cancer-type, response to anti-PD1/PDL1 checkpoint inhibitors seems associated with the absolute levels of pre-existing cytotoxic T-cell response.

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Abstract Details

Meeting

2016 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Developmental Therapeutics—Immunotherapy

Track

Developmental Therapeutics and Translational Research

Sub Track

Biomarkers and Correlative Studies from Immunotherapy Trials

Citation

J Clin Oncol 34, 2016 (suppl; abstr 3033)

DOI

10.1200/JCO.2016.34.15_suppl.3033

Abstract #

3033

Poster Bd #

355

Abstract Disclosures

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