Abstract IA12: Integrative genomics and immune contexture approach to immuno-oncology

Abstract

Abstract To date the anatomic extent of tumor (TNM classification) has been by far the most important factor to predict the prognosis of cancer patients. However, this classification provides limited prognostic information and does not predict response to therapy. We showed that tumors from human colorectal cancer with a high density of infiltrating memory and effector-memory T-cells (Tem) are less likely to disseminate to lymphovascular and perineural structures and to regional lymph nodes. We demonstrated the critical tumor-microenvironment parameters determining the dissemination to distant metastasis. We showed that the combination of immune parameters associating the nature, the density, the functional immune orientation, and the location of immune cells within the tumor was essential to accurately define the impact of the local host-immune reaction on patient prognosis. We defined these parameters as the “immune contexture.” We characterized the immune landscape within human tumors, and showed the importance of adaptive immune cells including cytotoxic T cells, Th1 cells, B cells, and T follicular-helper (Tfh) cells. We described the immunopenotype and antigenome associated with immune escape mechanisms and demonstrated mechanisms associated with preexisting and proliferating intratumoral T cells. Based on the immune contexture, a standardized, simple, and powerful digital pathology-based immune stratification-system, termed Immunoscore, was delineated having a prognostic power superior to that of the currently used cancer staging system. Tumor invasion parameters were statistically dependent on the host-immune reaction. A worldwide Immunoscore consortium validated the prognostic value of Immunoscore, using a standardized assay. Recent data are supporting the significant role of Immunoscore within lung, liver, and brain metastases. Thus, tumor progression, invasion, and recurrence are dependent on preexisting immunity and on Immunoscore, and the role of the immune contexture in predicting response to immunotherapy will be discussed. Citation Format: Jérôme Galon. Integrative genomics and immune contexture approach to immuno-oncology [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr IA12.