Nov 17, 2014

Immune Landscape and Immunoscore in the Era of Cancer Immunotherapies

Dr. Jérôme Galon, Research Director, INSERM, Head of Integrative Cancer Immunology Laboratory, INSERM, Paris, France

To date the anatomic extent of tumor, TNM classifications, has been by far the most important factors to predict the prognosis of cancer patients. However, this classification provides limited prognostic information in estimating the outcome in cancer and does not predict response to therapy.
Using large-scale technologies, quantitative measurements, and integrative biology approaches we evaluated the importance of the host-immune response within human tumors.
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 showed that the combination of immune parameters associating the nature, the density, the functional orientation and the location of immune cells within the tumor was essential to accurately define the impact of the local host immune reaction on patients’ prognosis. We defined these parameters as the “immune contexture”, and factors modulating it will be discussed. We recently characterize 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. Analysis of chromosomal instability revealed mechanisms associated with intratumoral lymphocyte proliferation. Based on the immune contexture, a standardized, simple and powerful immune stratification system, termed “Immunoscore”, was delineated that may bear 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 is testing the prognostic value of Immunoscore, using a standardized assay to routinely measure the immune status of a cancer patient.
The functional orientation of the immune contexture is characterized by immune signatures qualitatively similar to those predicting response to immunotherapy, Thus, the continuum of immune response existing, spanning a balance between tumor cell growth and elimination, will be discussed.