Immune checkpoint expression on peripheral lymphocytes in cervical cancer patients: moving beyond the PD-1/PD-L1 axis

Abstract In recent years, immune checkpoint therapy to reverse NK and T cell exhaustion has emerged as a promising treatment in various cancers. Recently, the FDA has approved anti-PD-1 pembrolizumab for patients with recurrent or metastatic cervical cancer. Other checkpoint molecules, such as TIGIT and Tim-3 have yet to be fully explored in this disease. Here, we found that PD-1, TIGIT, and Tim-3 are over-expressed on some peripheral blood CD56dim and CD56bright NK cells and T cells in cervical cancer patients and women with premalignant lesions. However, we observed stronger significance and separation between groups when these three molecules were examined together. These cells, with an apparently “exhausted” phenotype, were significantly augmented in patients. Different PD-1 levels (PD1low, PD1int, PD-1hi) on T cells were used to further define checkpoint positive populations. Soluble PD-L1 was observed to be increased in cervical cancer. Within the cancer group, the highest levels of sPD-L1 and triple positive or double positive cells and tumor stage were found similarly within tumors of different stages. Our results might show an overview of what is happening in patients with precancerous lesions and cervical cancer, and may give an early clue as to whom to administer monoclonal checkpoint blocking therapies.