Decoding the Complexity of Immune–Cancer Cell Interactions: Empowering the Future of Cancer Immunotherapy

SIMPLE SUMMARY: Cell-to-cell communication between the immune system and tumors is of the utmost importance; it influences the development of tumors, their growth, and how they respond to treatments. In this article, we provide an overview of why understanding the interactions between immune and tumor cells is so significant for developing anti-cancer therapeutics, particularly cancer immunotherapy. We delve into the methods and tools used to decipher these interactions and discuss the potential impact on the future of cancer treatment. Moreover, we emphasize the power of unraveling these interactions in advancing cancer immunotherapy. We also explore the challenges that can be tackled by gaining insights into these interactions. ABSTRACT: The tumor and tumor microenvironment (TME) consist of a complex network of cells, including malignant, immune, fibroblast, and vascular cells, which communicate with each other. Disruptions in cell–cell communication within the TME, caused by a multitude of extrinsic and intrinsic factors, can contribute to tumorigenesis, hinder the host immune system, and enable tumor evasion. Understanding and addressing intercellular miscommunications in the TME are vital for combating these processes. The effectiveness of immunotherapy and the heterogeneous response observed among patients can be attributed to the intricate cellular communication between immune cells and cancer cells. To unravel these interactions, various experimental, statistical, and computational techniques have been developed. These include ligand–receptor analysis, intercellular proximity labeling approaches, and imaging-based methods, which provide insights into the distorted cell–cell interactions within the TME. By characterizing these interactions, we can enhance the design of cancer immunotherapy strategies. In this review, we present recent advancements in the field of mapping intercellular communication, with a particular focus on immune–tumor cellular interactions. By modeling these interactions, we can identify critical factors and develop strategies to improve immunotherapy response and overcome treatment resistance.