HAVCR2 and cancer: In the present study, we first observed that Tim-3 and PD-1 expression was up-regulated on circulating CD8+ T cells in CRC patients, a finding consistent with previously study that the expression of PD-1 is significantly higher in patients with cancer relative to the levels in healthy controls, such as T-follicular helper cells lymphoma [25], head and neck cancer [26], oral squamous cell carcinoma [27], and ovarian cancer [28].