In CLL, where PD‐1 ICB does not induce clinical responses, CXCR5+PD‐1+ CD8 T cells show increased differentiation ex vivo, and altered differentiation toward effector populations after stimulation, indicating that functional modulation by the CLL microenvironment could hamper responses to PD‐1 ICB. Here, CD8A is linked to B-cell chronic lymphocytic leukemia.