PD-L1 expression in colorectal cancer defines three subsets of tumor immune microenvironments

// Anna Maria Valentini 1 , Federica Di Pinto 1 , Filomena Cariola 2 , Vito Guerra 3 , Gianluigi Giannelli 4 , Maria Lucia Caruso 1 and Michele Pirrelli 1 1 Department of Pathology, National Institute of Gastroenterology “S. de Bellis”, Research Hospital, Castellana Grotte, Italy 2 Medical Genetic Unit, National Institute of Gastroenterology “S. de Bellis”, Research Hospital, Castellana Grotte, Italy 3 Department of Epidemiology, National Institute of Gastroenterology “S. de Bellis”, Research Hospital, Castellana Grotte, Italy 4 National Institute of Gastroenterology “S. de Bellis”, Research Hospital, Castellana Grotte, Italy Correspondence to: Anna Maria Valentini, email: am.valentini@irccsdebellis.it Keywords: colorectal cancer; microsatellite instability; immunohistochemistry; PD-L1; PD-1 Received: September 24, 2017 Accepted : December 05, 2017 Published: January 12, 2018 ABSTRACT Objectives: We investigated the PD-L1 expression in colorectal cancer (CRC) and in its microenvironment. Results: PD-L1 was expressed in neoplastic cells (NCs) and tumor-infiltrating immune cells (IICs). All samples PD-L1+ on NCs were also on IICs. Three types of cancers could be grouped: group A(NCs-/ IICs-); group B (NCs-/ IICs+); group C (NCs+/IICs+). To group A belong tumors characterized by poorly immunogenic competence, poor immune response but massive granulocyte infiltrate, justifying the absence of PD-L1 as an immunoinhibitor receptor. To Group B probably belong more immunogenic CRCs, justifying the strong IICs-mediated immune response, and up-regulation of PD-L1 expression only on IICs. To group C belong CRCs probably characterized by a large amount of tumor neoantigens resulting in a marked infiltration of lymphocytes and PD-L1 upregulation also in NCs. Materials and Methods: Sixty-three colorectal cancer specimens from a cohort of 61 patients were retrospectively reviewed. Thirty-seven MSS and 26 MSI-H CRCs enrolled in this study. Immunohistochemical staining to PD-L1 was performed by using MAb E1L3N. Conclusions: Our study calls attention to the importance to assess PD-L1 expression in tumor microenvironment also evaluating type and density of infiltrating immune cells to better stratify CRCs with different immunological patterns.