Characterization and Prognostic Impact of the Intra-Tumoral Immune Response in Human Cancers

In contrast to most cancers, infiltration of the primary tumor by memory CD8+ T cells is associated with poor prognosis in clear cell Renal Cell Carcinoma (ccRCC). We investigated the characteristics and the organization of the local immune response in Non Small Cell Lung Cancer (NSCLC) and in ccRCC. We showed that high density of mature DC present in Tertiary Lymphoid Structures (TLS-DC) correlates with good prognosis in both cancers. In NSCLC, the TLS-B-cell follicles are characterized by Ki-67⁺ proliferating germinal center B cells, surrounded by CD138 positive plasma cells. Follicular B cell density correlates with long term survival, both in patients with early- and advanced-stage NSCLC. IgG and/or IgA specific for different tumor-associated antigens (TAA) were produced by tumor-infiltrating B cells cultured in vitro. We further characterized the microenvironment of ccRCC primary tumors and revealed associations between an extensive CD8+ T cell infiltrate, high expression of immunoregulatory molecules and poor prognosis. Interestingly, most of the DC were located outside TLS, and were MHC Class II low and CD83 negative, suggesting that they correspond to not fully mature DC. Their density correlated with poor prognosis. Altogether our findings highlight the pivotal function of DC and TLS in shaping an effector and memory immune response mediated by T and B cells against cancer.