Boosting immune responses in lung tumor immune microenvironment: A comprehensive review of strategies and adjuvants

The immune system has a substantial impact on the growth and expansion of lung malignancies. Immune cells are encompassed by a stroma comprising an extracellular matrix (ECM) and different cells like stromal cells, which are known as the tumor immune microenvironment (TIME). TME is marked by the presence of immunosuppressive factors, which inhibit the function of immune cells and expand tumor growth. In recent years, numerous strategies and adjuvants have been developed to extend immune responses in the TIME, to improve the efficacy of immunotherapy. In this comprehensive review, we outline the present knowledge of immune evasion mechanisms in lung TIME, explain the biology of immune cells and diverse effectors on these components, and discuss various approaches for overcoming suppressive barriers. We highlight the potential of novel adjuvants, including toll-like receptor (TLR) agonists, cytokines, phytochemicals, nanocarriers, and oncolytic viruses, for enhancing immune responses in the TME. Ultimately, we provide a summary of ongoing clinical trials investigating these strategies and adjuvants in lung cancer patients. This review also provides a broad overview of the current state-of-the-art in boosting immune responses in the TIME and highlights the potential of these approaches for improving outcomes in lung cancer patients.