PD-1 Ligand Expression in Epithelial Thyroid Cancers: Potential Clinical Implications

Abstract

The new immunotherapy targeting the programmed cell death 1 (PD-1) receptor and its cognate ligand PD-L1 has renewed hopes of eradicating the most difficult human cancers to treat. Among these, there are the poorly differentiated and anaplastic thyroid cancers, unresponsive to all the therapies currently in use. In the present review we will summarize information regarding the expression of PD-L1 in the different thyroid cancer histotypes, its correlation with clinicopathological features, and its potential prognostic value. Then, we will evaluate the available data indicating the PD-1/PD-L1 axis as a promising target for thyroid cancer therapy.

PD‐L1 and thyroid cytology: A possible diagnostic and prognostic marker

“…As reported in other publications, we explored the possibility of a link between PD-L1 and BRAF V600E. 45,46,48,[58][59][60][61] Angell et al observed that BRAF V600E mutation was associated with immunosuppressive mechanisms in PTC, including PD-L1 expression. 45 According to published reports, the rate of PD-L1 expression is qualitatively and quantitatively higher in BRAF V600E-mutated thyroid lesions, even up to 53% in 1 study.…”

Do we need PD‐L1 as a biomarker for thyroid cytologic and histologic specimens?

“…The limited retrospective data available to date suggest that PD-L1 could represent a prognostic marker for patients with thyroid cancer 17 and that anti-PD-1/PD-L1 therapies could be an option for a very limited subset of patients who have aggressive thyroid cancers (PDTC or ATC) that are resistant to the currently available therapies. 1,[6][7][8]21 Provided cytologic samples are deemed adequate for PD-L1 testing, whether the information provided by this test will be clinically useful preoperatively is doubtful, and many issues remain to be addressed. It is also likely that a single test such as PD-L1 immunohistochemistry cannot be used as a reliable surrogate to predict the efficiency of immunotherapy and that taking into account other important components that affect complex and dynamic tumor-immune interactions will be required.…”

“…Although chronic inflammation is a well known risk factor for tumor initiation and promotion, the ability of cancer cells to avoid the immune damage by disabling components of the host immune system is now considered a hallmark of cancer. In cancer, the immune response is turned off by various mechanisms, including: 1) inactivation of cytotoxic T lymphocytes and natural killer cells by secreting immunosuppressive factors; 2) recruitment of immunosuppressive cells (eg, myeloid‐derived suppressor cells, regulatory T cells); and 3) expression of inhibitory ligands for the immune checkpoint receptors, including CTLA‐4 (cytotoxic T‐lymphocyte associated protein 4) and PD‐L1 (programmed death‐ligand 1) . Therefore, the complex interactions between immune cells and tumor cells play a major role in tumor development, including tumor growth, invasion, and metastasis, and subsequent patient outcomes .…”

“…Several recent studies have explored the role of the PD‐1/PD‐L1 axis in neoplastic and nonneoplastic thyroid diseases (for a review, see Ulisse et al). Most studies investigating PD‐L1 in thyroid cancer have evaluated its prognostic relevance by correlating PD‐L1 expression levels with clinicopathologic features, whereas some studies have evaluated the diagnostic value of PD‐L1 in thyroid cancer.…”

“…1,21 Preclinical studies have PD-L1 Biomarker for Thyroid Specimens/Pusztaszeri et al demonstrated the efficacy of PD-1/PD-L1 axis blockade in limiting the growth of ATC-derived cell lines injected into mice, 1 but data from clinical trials with anti-PD-1/PD-L1 drugs for aggressive thyroid cancers have been limited and rather disappointing. 1,[6][7][8] In a retrospective study from The University of Texas MD Anderson Cancer Center, 12 patients with ATC received pembrolizumab in combination with kinase inhibitors at the time of disease progression. Of these patients, 5 had a partial response, 4 had stable disease, and 3 had progressive disease.…”