Abstract
ObjectivesWe investigated the PD-L1 expression in colorectal cancer (CRC) and in its microenvironment.ResultsPD-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 MethodsSixty-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.ConclusionsOur 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.
Highlights
Colorectal carcinogenesis is driven by sequential genetic and epigenetic alteration of epithelial cells and is influenced by tumor-host interaction [1,2,3]
PD-L1 was expressed in neoplastic cells (NCs) and tumor-infiltrating immune cells (IICs)
To group C belong colorectal cancer (CRC) probably characterized by a large amount of tumor neoantigens resulting in a marked infiltration of lymphocytes and PD-L1 upregulation in NCs
Summary
Colorectal carcinogenesis is driven by sequential genetic and epigenetic alteration of epithelial cells and is influenced by tumor-host interaction [1,2,3]. A well-known example of this interaction is the strong histological reaction of tumor infiltrating lymphocytes (TILs) that globally constitute a robust prognostic parameter of favorable clinical outcome in colorectal cancer (CRC) patients, acting as the gatekeepers in preventing tumor dissemination [4]. Tumors are rarely rejected spontaneously, because of their ability to create an immunosuppressive microenvironment through the activation of immune checkpoints such as PD-L1, CTLA-4, LAG-3, TIM-3 [5]. PD-1 is an immune-inhibitory receptor that is constitutively expressed by activated T lymphocytes and macrophages whereas other non-T lymphocytes, such as B www.impactjournals.com/oncotarget cells and natural killer cells, express PD-1 only on induction [9, 10]. High levels of expression of PD-1 are induced on T lymphocytes as a result of persistent inflammatory stimuli that determine their exhaustion or anergy [11]
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