Turning cold tumors hot: Strategies to enhance antitumor immunity

Immunologically cold tumors remain a major obstacle to effective cancer immunotherapy because they lack sufficient immune infiltration and fail to sustain productive antitumor immune responses. Although substantial progress has been made in understanding the mechanisms underlying immune evasion, only a minority of patients achieve durable benefit from current immunotherapeutic approaches. In this review, we discuss emerging strategies aimed at converting cold tumors into immune-responsive lesions by enhancing tumor antigenicity and promoting effective immune priming. We examine how these approaches may cooperate with interventions that induce immunogenic cell death, improve T cell trafficking, reverse immunosuppression, and remodel the tumor microenvironment. We further discuss advanced synthetic immunotherapeutic strategies designed to overcome multiple layers of immune resistance. Collectively, current evidence suggests that no single mechanism is sufficient to drive durable cold-to-hot tumor conversion, highlighting the need for integrated therapeutic approaches capable of simultaneously targeting distinct biological barriers to antitumor immunity.