Activated platelets stimulate effector CD8+ T cells to enhance HNSCC immunotherapy efficacy.

Programmed Death Receptor-1 (PD-1) is an immune checkpoint receptor expressed on the surface of T cells. Monoclonal antibodies targeting PD-1 and its ligand, PD-L1, are among the most widely utilized immune checkpoint inhibitors in cancer immunotherapy, dramatically improving the prognosis of patients with various malignancies. Traditionally, platelets, which are cytoplasmic fragments derived from megakaryocytes, have been primarily recognized for their roles in hemostasis and coagulation. However, recent studies have highlighted the emerging role of platelets in cancer biology and therapy. Platelets can modulate immune cell functions through various mechanisms, including the release of bioactive molecules and direct interactions with immune cells. A deeper understanding of the interplay between platelets and immune responses could pave the way for novel therapeutic strategies in cancer treatment. In our research, in patients with better treatment responses, there are higher levels of mature and activated CD8+ T cells in their PBMCs prior to treatment. Additionally, the activation of platelets is also more pronounced, and the proteins expressed on these platelets may modulate immune cells. After receiving immunotherapy, patients in the responsive (R) group exhibited a higher abundance of activated effector CD8+ T cells, which demonstrated stronger immune response capabilities. Furthermore, the increased levels of activated platelets in the R group may contribute to the regulation of CD8+ effector memory T cells, influencing their quantity and function. Our study suggests that the functional state of CD8+ T cells and the level of activated platelets prior to treatment may serve as predictive indicators for the efficacy of PD-1 inhibitors in head and neck cancer patients. Activated CD8+ effector T cells may contribute to the differences in immunotherapy responses, with activated platelets playing a role in promoting the maturation and activation of CD8+ effector memory T cells.These insights help better understand the interactions between platelets and immune cells, particularly emphasizing the role of CD8+ effector memory T cells in immunotherapy. Additionally, they offer potential strategies for predicting patient responses to PD-1 inhibitor treatment and optimizing the efficacy of immunotherapy.