Decoding the Interplay: Exploring Immunotherapy Resistance in the Tumor Microenvironment

The tumor microenvironment (TME) surrounds the tumor and includes blood vessels, immune cells, fibroblasts, signaling molecules, and the extracellular matrix. This review examines the cellular components and pathways within the TME, highlighting their potential as targets for immunotherapy. It also covers recent advances from the past several years in TME, immunotherapy, and combination therapy. The review emphasizes the role of CD8+ T cells in the TME and their relevance to immunotherapy. It discusses various T cell-targeted treatments, including PD-1/PDL1, CTLA-4, VEGF, Interferon-ɣ, LAG-3, and ER stress-XBP1. Recognizing the complexity and uniqueness of each tumor's immunotherapy network, the review aims to understand and compare the TMEs of different cancers and the respective immunotherapies. Cancers covered include non-small cell lung Cancer (NSCLC), pancreatic ductal adenocarcinoma (PDAC), cervical cancer, chronic lymphocytic leukemia, and gastric cancers. The review also addresses future research directions and applications of immunotherapies, aspiring to advance TME understanding and research.