Enhanced programmed death 1 (PD-1) and PD-1 ligand (PD-L1) expression in patients with actinic cheilitis and oral squamous cell carcinoma

Abstract

PD-1 and PD-L1 can be involved in tumor escape, and little is known about the role of these molecules in oral tumors or pre-malignant lesions. In the present study, we investigated the expression of PD-1 and PD-L1 in the blood and lesion samples of patients with actinic cheilitis (AC) and oral squamous cell carcinoma (OSCC). Our results showed that lymphocytes from peripheral blood and tissue samples exhibited high expression of PD-1 in both groups analyzed. Patients with AC presented higher percentage as well as the absolute numbers of CD4+PD-1+ and CD8+PD-1+ lymphocytes in peripheral blood mononuclear cells (PBMC) than healthy individuals, while patients with OSCC presented an increased frequency of CD8+PD1+ in PBMC when compared with controls. On the other hand, increased frequency of CD4+ and CD8+ T cells expressing PD-1(+) accumulate in samples from OSCC, and the expression of PD-L1 was intense in OSCC and moderate in AC lesion sites. Lower levels of IFN-γ and higher levels of TGF-β were detected in OSCC samples. Our data demonstrate that PD-1 and PD-L1 molecules are present in blood and samples of AC and OSCC patients. Further studies are required to understand the significance of PD-1 and PD-L1 in oral tumors microenvironment.

Circulating and tumor-infiltrating Tim-3 in patients with colorectal 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 ]. Next analysis showed that Tim-3 + PD-1 + CD8 + T cells in CRC patients are significantly higher than that in healthy donors.…”

Transient immunological and clinical effectiveness of treating mice bearing premalignant oral lesions with PD‐1 antibodies

“…However, studies with animal models and cancer patients have also shown that combining antibody blockade of the PD‐1/PD‐L1 axis with other forms of immunotherapy can lead to more meaningful clinical responses 32, 33, 34, 35. Approaches to block checkpoint signals have not been previously tested for their capacity to prevent premalignant lesion progression to cancer, despite indications of subjects with premalignant lesions having increased expression of PD‐L1 and PD‐1 + cells36, 37. The current study tested the immunological and clinical effects of PD‐1 blocking antibody treatment in a mouse 4NQO carcinogen‐induced premalignant oral lesion model that progresses to oral cancer.…”

“…One such study showed increased expression of PD‐L1 within premalignant respiratory papillomas and suggested that this was indicative of immune exhaustion 36. Results of a study of patients with actinic cheilitis, an oral premalignant lesion that can progress to oral cancer, showed increased levels of PD‐1 + cells within the peripheral blood compared to that seen for controls, although levels were greater within the cancer tissue compared to levels in the premalignant lesions 37. Also shown in this study was PD‐L1 expression within premalignant lesions, although PD‐L1 expression was greater within HNSCC tissues.…”

Immunotherapies: The Blockade of Inhibitory Signals

“…Up-regulation of PD-1 correlates with the prognosis of HCC (hepatic cell carcinoma) patients and raises the rate of recurrence 54, 55. A recent research demonstrated enhanced PD-1 expression in actinic cheilitis and oral squamous cell carcinoma 56. It is highly likely that the impairment of tumor-infiltrating T lymphocyte functions is due to the expression of PD-1 on the effector cells 57.…”