Characterising and Evaluating the Immune Microenvironment Landscapes of Colorectal Cancer Shaped by Different Therapies

Colorectal cancer (CRC) occurs as the third most common cancer with high mortality across the world. Understanding the intratumoral immune cell heterogeneity and their responses to various therapies is crucial for enhancing patient outcomes. This study aimed to characterise and evaluate the immune microenvironment landscapes of CRC shaped by different therapies including CD73 inhibitor, PD-1 blockade and photothermal therapy (PTT). Our investigation revealed that three therapies could commonly modulate the down-regulation of Treg, M2 macrophage and Ptprj+ G4 granulocyte, up-regulation of effector/memory T cell, M1 macorphage and Hilpda+ G1 granulocyte. Moreover, we identified the uniquely dis-regulated cell types and pathway activities response to each therapy, such as CD73 inhibitor enriched more Cd8+ memory and central memory (CM) cell, PD-1 blockade with more Cd8+ CTL and Cxcl3+ G2 granulocyte, and PTT with more Cd8+ effector memory and Rethlg+ G3 granulocyte cell. These responses disordered the glycolysis, angiogenesis, phagocytosis functions and cellular communication to reshape the CRC tumour immune microenvironment. We provide the detail insights into the intratumoral immunomodulation preferences of CRC mice treated with CD73 inhibitor, PD-1 blockade and PTT therapies, which might contribute to the ongoing development of more effective anticancer strategies.