Tumor Microenvironment Regulates Immune Checkpoints: Emerging Need of Combinatorial Therapies

Purpose of Review The tumor microenvironment (TME) acts as a protagonist in the regulation of immune-mediated checkpoints, which contributes to cancer cell immune evasion. This study investigates the dynamic interactions within the TME, with an emphasis on immune checkpoint modulation as a critical mechanism for tumor immune evasion. We investigate the rationale for concurrently targeting numerous checkpoints in order to restore and strengthen anticancer immunity. By comprehensively assessing the current state of research, we highlight the emerging need for integrated immunotherapeutic strategies that address the complex TME-mediated regulation of immune checkpoints, ultimately offering more effective and durable treatment options for cancer patients. Recent Findings. Novel checkpoints such as the B7-H3, B7-H4, and drugs targeting CD73 and SIRPα are being extensively explored. Targeting these checkpoints has reduced the tumor burden by targeting the tumor microenvironment. Summary We have briefly outlined the tumor microenvironment and the complex signaling cascade it undertakes to fuel cancer growth thereby prompting the need to target the tumor microenvironment through novel checkpoints thus providing tailor-made therapeutic strategies.