Influence of Tumor Location on the Composition of Immune Infiltrate and Its Impact on Patient Survival. Lessons from DCBCL and Animal Models

Diffuse large B-cell lymphomas (DLBCLs) are heterogeneous diseases growing either in nodal or extranodal locations including the central nervous system. One key issue is to decipher the prognostic value of immune cells infiltrating these tumors as DLBCLs developing in sanctuaries are more aggressive than nodal DLCBLs. Here, we summarize available data from the literature regarding the prognostic values of the different immune cell types found in these two types of human primary tumors (i.e., nodal vs brain). In nodal DLBCLs, memory T-cells and dendritic cells (DCs) densities are of good prognostic value whereas the influence of regulatory T-cells (Tregs) is less clear, in accordance with other types of cancers. Data for primary central nervous system lymphomas are very sparse for these cell types. By contrast, CD8(+) cytotoxic T-cells seem to be of poor prognosis in either location. Their presence is linked to a loss of MHC expression providing a possible immune escape mechanism for these tumors. Clearly, tumor-associated macrophages are not associated to a significant prognostic value even in the brain where they highly infiltrate the tumor. Animal models indicate some specific features of lymphoma developing in sanctuaries by comparison to splenic location, with a higher infiltration of Tregs and less DCs, most likely reflecting the immunosuppressive context of these organs. All these informations illustrate the high impact of the immune system on patient outcome, encourage the pursuit of the immune environment's analysis and of immunotherapeutic approaches.