Correlation of immune profiling and exceptional response to immune checkpoint inhibitor in a patient with head and neck cancer.

Abstract

Abstract: Immune checkpoint inhibitors (ICIs) have revolutionized the field of cancer therapy and it is a huge step forward in the treatment of various cancers including head and neck cancer. Nivolumab, an anti-PD-1 monoclonal antibody, reportedly has improved overall survival in head and neck cancer, yet only a subset of patient population benefit from it. Tissue-based markers such as PD-L1expression positive, tumor mutation burden-high, and microsatellite instability-high are widely believed to be a biomarker for ICIs such as nivolumab in solid tumors. However, due to the low prevalence of microsatellite instability-high and tumor mutation burden-high in most cancers and PD-L1 negative tumor responding well to ICIs, it tends to be insufficient to identify whether patients should receive ICIs as per this biomarker alone. Mechanism of response to checkpoint inhibitor therapy is unclear and hence studying the role of immune cells and pathways involved is important. The role played by peripheral blood parameters remains ambiguous. Here in, we present a case of an 85-year-old patient with advanced carcinoma buccal mucosa who was treated with Nivolumab after failure of chemotherapy and radiotherapy. Considering the limitations of tissue-based biomarkers to predict response to ICIs, we aimed to identify which blood-based biomarkers correlated with the response to treatment and monitored the immune parameters and serum cytokine levels during the course of Nivolumab. Here in, we also describe the clinical presentation of patient during the course of this therapy. Blood samples were collected pretherapy and post-therapy to monitor the response. Both clinical and immunological differences in the composition of Ki67+ PD-1+ CD8 T cells, Granzyme B+ CD8 T cells, NK and NKT cells, and serum cytokine levels of TNF alpha were observed to be elevated post-ICIs during monitoring of the patient receiving checkpoint inhibitor therapy. Monitoring these circulating peripheral blood markers in wider population of patients receiving ICI therapy, during its course, may provide a perspective in the development of new biomarkers for predicting response and may serve as a basis for personalized treatment. This case report describes valuable insights into evolution of immune markers predicting and monitoring response to Nivolumab in a patient with cancer.