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.
Highlights
Studies have shown that the PD-1/PD-L1 immunomodulatory pathway slows down anti-tumor immunity in a number of cancers
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
Summary
Studies have shown that the PD-1/PD-L1 immunomodulatory pathway slows down anti-tumor immunity in a number of cancers. Since 2012, the Lower Anogenital Squamous Terminology (LAST) [3] recommended denomination for HPV-associated squamous lesions of the lower anogenital tract as low-grade and high-grade squamous intraepithelial lesion (LSIL and HSIL respectively). Oncogenic HPV infection plays a crucial role in developing both cervical and anal lesions, by integration of the viral DNA into the epithelial cells and activation of oncogenic early proteins E6 and E7. This causes downregulation of suppressing tumors genes, especially TP53 and Rb, and upregulation of p16 [5]. The aim of our study was to explore PD-1/PD-L1 pathway and immune infiltration in a prospective cohort of patients presenting anal intraepithelial neoplasia of different grades
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