Abstract 1464: The tumor immune microenvironment is similar in anal squamous cell carcinomas (SCCs) from HIV-infected and uninfected patients
Authors: Yanik Elizabeth L. , Topalian Suzanne L. , Kaunitz Genevieve , Esandrio Jessica , Cottrell Tricia , Taube Janis M. 
Published: July 2016

Abstract
Tumors may evade immune attack by constitutive (oncogene-driven) and/or adaptive (IFN-g inducible) expression of PD-L1. PD-1/PD-L1 blockade can mediate tumor regression in immunocompetent patients. In HIV-infected patients, developing tumors may face little immune selection pressure and therefore may not evolve to evade immune attack. Expression of PD-L1 has not been systematically assessed in cancers from HIV-infected people. In the current study, immunohistochemistry for PD-L1, and CD3 and CD68 (immune cells, ICs) was performed on biopsies from 46 anal SCCs, including 27 from HIV-infected and 19 from uninfected patients. The proportion of cases with tumor cell PD-L1 expression was similar in patients with and without HIV (52% vs. 47%, respectively, p = 0.76), as was the presence of moderate/severely dense ICs (33% vs. 37%, p = 0.81) (Table). Among HIV-infected patients, 19% of anal SCC tumors (5/27) both expressed PD-L1 and had moderate/severe IC infiltration. Tumors from HIV-infected and uninfected patients had similar densities of CD68+ macrophages (mean 517 vs. 404 cells/mm2, p = 0.33) and CD3+ T- lymphocytes (mean 501 vs. 428 cells/mm2, p = 0.57). A component of adaptive PD-L1 expression (juxtaposed to tumor infiltrating ICs) was also observed in both groups (56% vs. 47%, p = 0.58), consistent with comparable T-cell functionality. Further studies will explore the expression of other immune checkpoint proteins and lymphocyte subsets. Despite expectations that cancers from HIV-infected patients would show reduced inflammation, our preliminary findings demonstrate an immune-reactive microenvironment in both HIV+ and HIV- anal SCCs and suggest that anti-PD-1/PD-L1 therapies should be evaluated in anal SCC patients. Tumor infiltrating ICTotalHIV- a (n = 19)HIV+ a (n = 27)P-value cNone-mildTotal3012 (40%)18 (60%)0.66PD-L1(+) b145 (36%)9 (64%)PD-L1(-)167 (44%)9 (56%)Moderate-severeTotal167 (44%)9 (56%)0.95PD-L1(+) b94 (44%)5 (56%)PD-L1(-)73 (43%)4 (57%)a Anal SCC tumors in HIV-infected patients include 19 tumors identified through the AIDS-Cancer Specimen Resource and 8 tumors identified at Johns Hopkins Hospital. Anal SCC tumors in HIV-uninfected patients include 1 tumor identified through the AIDS-Cancer Specimen Resource and 18 tumors identified at Johns Hopkins Hospital.b Defined as ≥5% of tumor cells expressing cell surface PD-L1 by immunohistochemistry with the 5H1 monoclonal antibody.c P-values are for the comparison of PD-L1 expression between HIV+ and HIV- anal SCCs within strata of tumor infiltrating ICIC = immune cells
Citation Format: Elizabeth L. Yanik, Suzanne L. Topalian, Genevieve Kaunitz, Jessica Esandrio, Tricia Cottrell, Janis M. Taube. The tumor immune microenvironment is similar in anal squamous cell carcinomas (SCCs) from HIV-infected and uninfected patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1464.