New insights into the interaction of the immune system with non-small cell lung carcinomas.

The basis of current and future lung cancer immunotherapy depends mainly on our knowledge of the molecular mechanisms of interactions between cancer and immune cells (ICs), as well as on interactions occurring between the different populations of intra-tumor ICs. These interactions are very complex, as virtually all immune cell types, including macrophages, neutrophils, mast cells, natural killer (NK) cells, dendritic cells and T and B lymphocytes can infiltrate lung cancer tissues at the same time. Moreover these interactions lead to progressive emergence of an imbalance in ICs. Initially ICs have an anti-tumor effect but then induce immune tolerance and eventually tumor progression and dissemination. All the cells of innate and adaptive intra-tumor immunity engage in this progressive phenotypic switch. A majority of non-small cell lung carcinoma (NSCLC) patients do not benefit from the expected positive responses associated with current immunotherapy. Thus, there is urgent need to better understand the different roles of the associated cancer ICs. This review summarizes some of the new insights into this domain, with particular focus on: the myeloid cell population associated with tumors, the tertiary lymphoid structures (TLSs), the role of the P2 purinergic receptors (P2R) and ATP, and the new concept of the "liquid microenvironment" implying blood circulating ICs.