Immune microenvironentEstrogen• Estradiol reverses immunosuppressive TME by downregulating PD-L1  expression and modulating the population of infiltrating immune cells and  tumor-associated cells.• Estradiol reduces immunosuppressive factor level in EVs and inhibits MC38  colon tumor growth.• Combined treatment with estradiol and αPD-L1 increase the abundance of  intestinal probiotics (P. goldsteinii and L. murinus) while decreasing the  presence of opportunistic pathogens (Enterobacteriaceae family). The gene discussed is CD274; the disease is colonic neoplasm.