PD-1/PD-L1 expression in anal squamous intraepithelial lesions

Abstract

Introduction: Studies have shown that the PD-1/PD-L1 immunomodulatory pathway slows down anti-tumor immunity in a number of cancers. The description of the expression of these molecules has never been performed in anal low-grade/ high grade squamous intra-epithelial lesions (LSIL/HSIL respectively). Materials and Methods: Patients followed in the AIN3 cohort were routinely sampled. For each selected sample, an immunohistochemical study was performed with anti-CD8, PD-1, PD-L1 antibodies. The presence and distribution of CD8+ lymphocytes, and the presence of PD-1+ lymphocytes and PD-L1+ epithelial cells were assessed. The comparison of these characteristics was performed between the HSIL and LSIL groups. Results: 33 patients were included and 78 samples selected (60 HSIL and 18 LSIL). CD8+ lymphocytes were observed more frequently in HSIL versus LSIL in the lamina propria or intra epithelial (respectively 90% vs. 60%, p = 0.01; and 62% vs. 33%, p = 0.04). PD-1+ lymphocytes were observed more frequently in HSIL versus LSIL (41% vs 11%, p = 0.03). There was no difference between HSIL and LSIL for PD-L1+ epithelial cells. Conclusions: Anal dysplastic lesions are accompanied by an inflammatory lymphocytic infiltrate expressing CD8 and PD-1, more frequent in high-grade lesions. These results highlight the involvement of the PD-1/PD-L1 pathway in the natural history of anal dysplasia.

PD‐L1 and PD‐1 expression in thyroid follicular epithelial dysplasia: Hashimoto thyroiditis related atypia and potential papillary carcinoma precursor

“…In our study, accompanying inflammatory cells were PD-L1 positive in all cases with at least 3% of positive cells in agreement with anal intraepithelial lesion analysis in accompanying inflammation (6-25% PD-L1 positivity according to low or highgrade dysplasia) [40]. PD-1 positive cells in more than 3% of cells were also found in all cases except one in FED group.…”

“…FED has been morphologically defined as dysplastic foci related to HT [10,11]. Recently, several studies on PD-L1 expression in various dysplastic tissues have emerged: such as oral mucosa [36,37], respiratory epithelium [38], Barrett's esophagus [39], and anal epithelium [40]. PD-L1 expression both in dysplastic epithelium and accompanying lymphocytes has been higher in high-grade lesions (12% and 25% positivity) in comparison with low-grade dysplastic anal lesions (6% and 6% positivity) [40].…”

“…Recently, several studies on PD-L1 expression in various dysplastic tissues have emerged: such as oral mucosa [36,37], respiratory epithelium [38], Barrett's esophagus [39], and anal epithelium [40]. PD-L1 expression both in dysplastic epithelium and accompanying lymphocytes has been higher in high-grade lesions (12% and 25% positivity) in comparison with low-grade dysplastic anal lesions (6% and 6% positivity) [40]. Nevertheless, comparison of various dysplastic lesions should take into account the variety of cancerogenesis in different localizations and cancer types, that is, virus and tobacco etiologies [38].…”

Human Immunodeficiency Virus Infection Promotes Human Papillomavirus-Mediated Anal Squamous Carcinogenesis: An Immunologic and Pathobiologic Review

“…PD-L1 expression in anal SCC has been linked with increased disease recurrence and decreased survival [119, 120]. Similarly, PD-L1 expression has been linked to the progression of precancerous lesions [121]. However, other studies have shown that PD-L1 expression indicates improved overall survival.…”

Simultaneous and Spatially-Resolved Analysis of T-Lymphocytes, Macrophages and PD-L1 Immune Checkpoint in Rare Cancers

“…On the other hand, tumor cells can evade immune anti-tumor response using several mechanisms, such as the expression of negative immune checkpoint molecules and the modulation of the tumor microenvironment [ 22 , 23 , 24 , 25 ]. The expression of PD-L1 has been demonstrated in penile [ 26 , 27 ], vulvar [ 28 , 29 ] and anal [ 30 , 31 ] carcinomas, with different percentages of positive cells, and these previous reports about PD-L1 expression, including TILs presence, in rare cancer tissues had been evaluated using a classic immunohistochemistry (IHC) [ 26 , 27 , 28 , 29 , 30 , 31 ]. Even though the IHC is considered as a hallmark for cancer diagnosis, this tool has several limitations, including inter-observer variability, and the fact that it only allows the analysis of one to two biomarkers at a time [ 32 ].…”