For a long time, cancer was understood as a disease progressing through successive stages, driven by dynamic genomic alterations leading to the malignant transformation of normal cells. Over the past two decades, this view has been substantially enriched: it is now established that the local immune infiltrate actively participates in shaping tumors. Early investigations showed that certain immune subpopulations infiltrating tumors, particularly cytotoxic T cells and memory T cells, are significantly associated with patient survival. The intratumoral immune context—defined by the type, functional orientation, density, and location of immune cells—thus emerges as a major determinant of clinical outcome.
To accurately describe these tumor–immunity dynamics, the authors integrated and analyzed multiple heterogeneous genomic and proteomic datasets, derived both from their own work and from public databases, conducting an in-depth exploration of the microenvironment in large cohorts of patients with colorectal cancer. A first decisive step consisted in standardizing the analysis of the immune infiltrate. Based on datasets covering purified subpopulations of innate and adaptive immune cells, compared with distant normal colon samples and colorectal cancer cells, the authors selected the most distinctive transcriptional profiles of each cell type. This compendium, named the Immunome, provides a reference enabling the identification of immune cells in complex tissues, whether healthy or pathological. Its application to the colorectal tumor microenvironment made it possible to propose the first immune landscape of tumors, illustrating the immune densities quantified at the center and the invasive margin of the tumor as well as their variations according to stage.
The Immunome has since been widely adopted to characterize the immune infiltrate in numerous cancers and other diseases, and was notably incorporated into the pan-cancer immunogenomic analysis of The Cancer Genome Atlas data, which revealed six stable immune subtypes associated with prognosis and with genetic and immunomodulatory alterations. Based on the most clinically relevant markers, those of T cells and cytotoxic T cells, a scoring system was developed, the consensus Immunoscore—the first internationally recognized standardized assay to quantify pre-existing immunity, validated with the support of the Society for Immunotherapy of Cancer. Patients with a high Immunoscore show the lowest risk of recurrence at five years, and this indicator outperforms the classical TNM classification in predicting clinical outcome.
Recognized as a hallmark of cancer in its own right, the immune component of the tumor microenvironment has thus acquired concrete diagnostic significance. The consensus Immunoscore has been introduced as an essential and desirable diagnostic criterion for colorectal cancer in the fifth edition of the WHO classification of digestive system tumors, as well as in the 2020 and 2021 ESMO clinical practice guidelines, in order to refine prognosis and adjust chemotherapy decisions.