Advances in cancer immunotherapy: historical perspectives, current developments, and future directions

Abstract

Cancer immunotherapy, encompassing both experimental and standard-of-care therapies, has emerged as a promising approach to harnessing the immune system for tumor suppression. Experimental strategies, including novel immunotherapies and preclinical models, are actively being explored, while established treatments, such as immune checkpoint inhibitors (ICIs), are widely implemented in clinical settings. This comprehensive review examines the historical evolution, underlying mechanisms, and diverse strategies of cancer immunotherapy, highlighting both its clinical applications and ongoing preclinical advancements. The review delves into the essential components of anticancer immunity, including dendritic cell activation, T cell priming, and immune surveillance, while addressing the challenges posed by immune evasion mechanisms. Key immunotherapeutic strategies, such as cancer vaccines, oncolytic viruses, adoptive cell transfer, and ICIs, are discussed in detail. Additionally, the role of nanotechnology, cytokines, chemokines, and adjuvants in enhancing the precision and efficacy of immunotherapies were explored. Combination therapies, particularly those integrating immunotherapy with radiotherapy or chemotherapy, exhibit synergistic potential but necessitate careful management to reduce side effects. Emerging factors influencing immunotherapy outcomes, including tumor heterogeneity, gut microbiota composition, and genomic and epigenetic modifications, are also examined. Furthermore, the molecular mechanisms underlying immune evasion and therapeutic resistance are analyzed, with a focus on the contributions of noncoding RNAs and epigenetic alterations, along with innovative intervention strategies. This review emphasizes recent preclinical and clinical advancements, with particular attention to biomarker-driven approaches aimed at optimizing patient prognosis. Challenges such as immunotherapy-related toxicity, limited efficacy in solid tumors, and production constraints are highlighted as critical areas for future research. Advancements in personalized therapies and novel delivery systems are proposed as avenues to enhance treatment effectiveness and accessibility. By incorporating insights from multiple disciplines, this review aims to deepen the understanding and application of cancer immunotherapy, ultimately fostering more effective and widely accessible therapeutic solutions. • Various aspects of immunotherapy, from its historical evolution to modern strategies and clinical applications, are explored. • Immunotherapeutic approaches, including cancer vaccines and oncolytic virus therapy, are discussed. • The efficacy and mechanisms of immune checkpoint inhibitors and adoptive cell therapies are evaluated. • The complexities of the tumor microenvironment and mechanisms of immune evasion are highlighted. • Advances in cytokines, chemokines, nanotechnology, and combination therapies that enhance immunotherapy effectiveness are outlined. • What are the primary strategies and modalities employed in cancer immunotherapy? • How does the tumor microenvironment influence the efficacy of cancer immunotherapy? • What are the key challenges in developing effective cancer vaccines and adoptive cell therapies? • How do molecular and genetic factors, including noncoding RNAs and epigenetic modifications, contribute to immunotherapy resistance? • What are the future directions for enhancing the efficacy and accessibility of cancer immunotherapy?