PD‑L1 expression and immune cells in anaplastic carcinoma and poorly differentiated carcinoma of the human thyroid gland: A retrospective study

Abstract

Anaplastic thyroid carcinoma (ATC) and poorly differentiated thyroid carcinoma (PDTC) have limited treatment options, and immune profiling may help select patients for immunotherapy. The prevalence and relevance of programmed death-1 ligand (PD-L1) expression and the presence of immune cells in ATC and PDTC has not yet been well established. The present study investigated PD-L1 expression (clone 22C3) and cells in the tumor microenvironment (TME), including tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs) and dendritic cells, in whole tissue sections of 15 cases of ATC and 13 cases of PDTC. Immunohistochemical PD-L1 expression using a tumor proportion score (TPS) with a 1% cut-off was detected in 9/15 (60%) of ATC cases and 1/13 (7.7%) of PDTC cases (P=0.006). PD-L1 expression in TILs was limited to the ATC group (73.3 vs. 0% in ATC and PDTC, respectively). In the ATC group, the TPS for tumor positive PD-L1 expression revealed a non-significant trend towards worse survival, but no difference was observed when investigating PD-L1 expression in TILs and TAMs. In addition to increased PD-L1 expression, all ATC cases exhibited significantly increased CD3 + and CD8 + T cells, CD68 + and CD163 + macrophages, and S100 + dendritic cells compared with the PDTC cases. Loss of mutL homolog 1 and PMS1 homolog 2 expression was observed in one ATC case with the highest PD-L1 expression, as well as in the only PDTC case positive for PD-L1. Notably, the latter was the only PDTC case exhibiting positivity for p53 and a cellular microenvironment similar to ATC. The current results indicated that PD-L1 expression was frequent in ATC, but rare in PDTC. In addition to PD-L1, the present study suggested that microsatellite instability may serve a role in both the TME and the identification of immunotherapy candidates among patients with PDTC.

Roles and new Insights of Macrophages in the Tumor Microenvironment of Thyroid Cancer

“…It is critical to evaluate their function and signaling pathways ( MacDonald et al, 2020 ). The infiltrating cells of ATCs include lymphocyte infiltrate (mainly CD8 + cytotoxic T cells) and TAMs ( Cameselle-García et al, 2021 ; Prete et al, 2021 ). M2-TAMs can secrete insulin-like growth factors (IGF) to activate IR-A/IGF1R and mediate PI3K/AKT/mTOR signaling pathway to accelerate ATC cells metastasis and enhance stem cell viability and stemness ( Lv et al, 2021b ).…”

Poorly Differentiated and Anaplastic Thyroid Cancer: Insights into Genomics, Microenvironment and New Drugs

“…Accordingly, Caillou et al showed that tumor-associated macrophages build up a dense network in whom cancer cells reside [102,103] and their presence is associated with a worse prognosis in ATC [104]. Cameselle-García and colleagues elucidated that ATC tumors are enriched of tumor infiltrating lymphocytes (mainly CD8+ cytotoxic T cells), which mainly reside in the interface between tumor ant thyroid tissue [105]. Otherwise, PDTC harbored less tumor infiltrating leukocytes compared to ATC, and presented a cold immune contexture in 65% of cases [101].…”

“…Otherwise, PDTC harbored less tumor infiltrating leukocytes compared to ATC, and presented a cold immune contexture in 65% of cases [101]. In these immune contexts, PD/PD-L1 pathway (programmed cell death protein-1/programmed cell death ligand-1) plays a crucial role in ATC and less frequently also in PDTC [97,105,106]. If in physiologic conditions, PD/PD-L1 pathway regulates T cell immune suppression, in neoplastic milieu it is exploited by cancer cells in order to avoid immune attack, by inducing T-cell exhaustion [107].…”

Comprehensive Analysis of the Prognosis and Drug Sensitivity of Differentiation-Related lncRNAs in Papillary Thyroid Cancer

“…Within the TME of TC, tumor cells interact with immune cell infiltration and coordinate the immune response that induces tumor dedifferentiation to promote PTC progression [ 22 , 23 , 24 ]. The proportions of immune cells, such as tumor-infiltrating lymphocytes, dendritic cells (DCs), and tumor-associated macrophages (TAMs), are closely related to the extent of differentiation [ 25 , 26 ]. Inhibition of intratumoral TAM recruitment might be able to restore RAI sensitivity in poorly differentiated TC [ 27 ].…”