Oncotarget

Research Papers:

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

Margot Bucau _, Nathalie Gault, Nanthara Sritharan, Emy Valette, Charlotte Charpentier, Francine Walker, Anne Couvelard and Laurent Abramowitz

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Oncotarget. 2020; 11:3582-3589. https://doi.org/10.18632/oncotarget.27756

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Abstract

Margot Bucau1, Nathalie Gault2,3, Nanthara Sritharan3, Emy Valette4, Charlotte Charpentier5,6, Francine Walker1, Anne Couvelard1,7 and Laurent Abramowitz4,8

1 AP-HP, Département de Pathologie, Hôpital Bichat-Claude Bernard, F-75018 Paris, France

2 AP-HP, Département d’Epidémiologie Biostatistiques et Recherche Clinique, Hôpital Bichat-Claude Bernard, F-75018 Paris, France

3 INSERM CIC-EC1425, Hôpital Bichat-Claude Bernard, F-75018 Paris, France

4 AP-HP, Service de Gastroentérologie et Proctologie, Hôpital Bichat-Claude Bernard, F-75018 Paris, France

5 AP-HP, Laboratoire de Virologie, Hôpital Bichat-Claude Bernard, F-75018 Paris, France

6 Université de Paris, INSERM UMR 1137 IAME, F-75018 Paris, France

7 Université de Paris, INSERM UMR 1149, F-75018 Paris, France

8 Ramsay GDS, Clinique Blomet, 75015 Paris, France

Correspondence to:

Margot Bucau,email: margot.bucau@aphp.fr

Keywords: anal dysplasia; PD-L1; HPV; anal cancer; immune microenvironment

Received: February 01, 2020     Accepted: September 10, 2020     Published: September 29, 2020

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.


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