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