Oncotarget

Research Papers:

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

Anna Maria Valentini _, Federica Di Pinto, Filomena Cariola, Vito Guerra, Gianluigi Giannelli, Maria Lucia Caruso, Michele Pirrelli

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Oncotarget. 2018; 9:8584-8596. https://doi.org/10.18632/oncotarget.24196

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Abstract

Anna Maria Valentini1, Federica Di Pinto1, Filomena Cariola2, Vito Guerra3, Gianluigi Giannelli4, Maria Lucia Caruso1 and Michele Pirrelli1

1Department of Pathology, National Institute of Gastroenterology “S. de Bellis”, Research Hospital, Castellana Grotte, Italy

2Medical Genetic Unit, National Institute of Gastroenterology “S. de Bellis”, Research Hospital, Castellana Grotte, Italy

3Department of Epidemiology, National Institute of Gastroenterology “S. de Bellis”, Research Hospital, Castellana Grotte, Italy

4National 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.


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