Dynamics of peripheral T populations after chemo- and/or radiotherapy in HNSCC patients

Head and neck squamous cell carcinoma (HNSCC) is a relevant medical issue since it is the sixth most common cancer globally and its incidence is increasing. It is is generally associated with a history of alcohol and tobacco consumption or abuse, and remarkable an etiopathogenetic correlation between tumor and Human Papilloma Virus (HPV). Surgery, radiotherapy and chemotherapy in various combinations are used in the treatment of head and neck cancers, depending on the TNM stage. Chemo-radiotherapy mechanisms of action against tumors considers the activation of anti-cancer immune response as a key event, since radiations act as a sort of "in situ vaccination”. Radiotherapy promotes the inflammation and subsequent activation of adoptive immune responses against tumor-associated antigens (TAA) released or expressed by the tumor. The peripheral immune response of 20 patients suffering for HNSCC was monitored using multiparametric flow cytometry in order to define the qualitative and quantitative characteristics of their immunological T cell response (CD4+ and CD8+ T lymphocytes maturation stage; cytokine production; regulatory commitment; expression of markers of exhaustion/IRs), before and after these subjects underwent chemo-radiotherapy treatment. The immunological monitoring data collected suggest an activatory effect on the immune system after therapy possibly due to the huge amount of cell death products acting as danger signals raised by chemotherapy-Rt combination and by the subsequent stimulation of cancer specific immune responses induced by antigen spreading. Peripheral blood samples of patients examined showed that therapy mainly induced a decrease of the CD3+ total T cell; the CD4+ T cells switched from the naïve to the late maturation stages cell subset expressing the PD-1 molecule, associated with an increase in secretion of Granzyme; on the CD8+ T cell compartment the therapy induced pro-maturation effects pushing them toward acquisition of full effector functions, suggested by the expansion of the CD8+CD28- T cell subset and by the decrease of the early maturation stages associated with the increase of Terminal Effector Memory CD8+ T.