Combining Vitamin D and Immune Checkpoint Blockade in Oral Cancer

Aparajita Verma

Aparajita presenting her work at a seminar.

Aparajita Verma presenting her work at a seminar.

Graduate Student Project

Introduction

Immunotherapy has shown promise in oral cancer patients. However, only a small number of patients (less than 15%) respond to this therapy alone, partially due to their weak immune system. Therefore, there is a need to identify new strategies to enhance the activity of immunotherapy against oral cancer. In this regard, calcitriol, an active form of vitamin D, has been shown to play a role in strengthening the immune system by increasing the number of T cells responsible for tumor destruction. However, the effect of calcitriol on the activity of immunotherapy has not been examined in oral cancer. My research in the lab of Dr. Mukund Seshadri at Roswell Park Comprehensive Cancer Center tries to understand the role of vitamin D on the activity of immunotherapy and whether vitamin D supplementation can improve the activity of immunotherapy against oral cancer.

Abstract

Immune checkpoint inhibitors (ICI), which block the interaction between programmed cell death protein 1 (PD-1) and its ligand (PD-L1), have led to dramatic improvements in outcomes for patients with oral squamous cell carcinoma (OSCC). However, only a small fraction of patients respond favorably to these agents highlighting the need for evaluating novel strategies that safely enhance its efficacy against OSCC. In this regard, calcitriol, the active metabolite of vitamin D, has been shown to increase intratumoral infiltration of T cells in preclinical models and OSCC patients. However, the impact of calcitriol on the response to ICI has not been examined in OSCC. To address this gap in knowledge, we developed a novel syngeneic murine model of OSCC to evaluate the effects of calcitriol in the context of ICI. Our results show that concurrent administration of calcitriol and ICI significantly delays tumor growth compared to controls and either monotherapy.

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