IL6 and colorectal carcinoma: It binds to the PD-L1 promoter, increasing PD-L1 expression in tumor and immune cells, which contributes to immune exhaustion via PD-1/PD-L1 interactions.117,118 Additionally, HIF-1α helps in immune escape by regulating various immune cells.118 For example, a recent study shows that microRNAs (miRNAs) are involved in hypoxia-induced treatment resistance in CRC through a feedback loop with HIF-1α, miR-338-5p, and IL-6.