Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.
It is well known that multiple hallmarks of aging including chronic inflammation (inflammaging) and decline in immune function (immunosenescence) can directly impact cancer progression and response to therapy. However, our understanding of the impact of age on the tumor immune microenvironment and response to immunotherapy in head and neck cancer remains limited. To address this gap in knowledge, we conducted experimental studies in syngeneic model of oral squamous cell carcinoma (OSCC). Non-invasive magnetic resonance imaging (MRI) in combination with flow/imaging mass cytometry-based multiplexing of the tumor immune microenvironment (TIME) was performed in orthotopic tumors established in old and young mice. Our results revealed that tumor growth was significantly accelerated in aged mice compared to young mice. Compared to tumors established in young hosts, cytometry by time-of-flight (CyTOF) analysis revealed a higher number of CD4+ FOXP3+ T regulatory cells, polymorphonuclear and monocytic myeloid-derived suppressor cells (P-MDSC and M-MDSC), and lower number of CD3+ T cells (including CD4+ and CD8+ T cells), subsets of central memory (Tcm) and effector memory CD8+ T cells (Tem). Aged mice did not respond to αPD-1 treatment (200 µg, Q2D x 3 doses), while young mice showed tumor regression. Tumors treated with αPD-1 in young mice showed a reduction in T cell exhaustion markers (PD-1, TIM3, LAG3), and an increase in granzyme B levels. However, these changes were not seen in tumors established in old mice treated with αPD-1. Collectively, our results demonstrate the impact of aging in promoting an immunosuppressive TIME in OSCC and resistance to immunotherapy. Investigation into the potential of senolytics to overcome these resistance mechanisms and promote OSCC response to immunotherapy is warranted.