Abstract
Downregulation of the T cell system has been proposed as a mechanism to block immunity in colonic cancer (CC). However, little has been studied about circulating αβ and γδ T cells and their immunological status in newly diagnosed patients. The aim of this study was to characterize the αβ and γδ T cell subsets in peripheral blood of patients with CC matched with healthy volunteers. In this prospective case-control study, blood samples were obtained from 96 patients with newly diagnosed treatment-naïve infiltrating colonic adenocarcinoma and 48 healthy volunteers. Pathological report at surgery was obtained from all CC patients. A significant decrease in CD3+ γδ T cells and CD3+CD8+ γδ T cells (p<0.001) were observed in CC patients. Apoptosis was significantly increased in all conventional and both αβ and γδ T cell subsets in patients with CC vs healthy subjects. γδ T cells were decreased in peripheral blood of patients with microscopic infiltration in tissues, history of cancer and synchronous colon cancer (p < 0.05). IFN-γ was significantly reduced in CC patients compared to controls. Cytotoxic effector γδ T cells TEMRA (CD8 and CD56) are the proportionally most abundant T cells in peripheral blood of CC patients. Patients with CC present a deep downregulation in the systemic T-cell immunity. These variations are evident through all tumor stages and suggest that a deficiency in γδ T cell populations could be preventing control of tumor progression. This fact prove the role of immunomodulation on CC carcinogenesis.
Highlights
Colorectal cancer (CRC) is the fourth most common cancer and the third cause of cancerrelated death worldwide [1]
We found a significant decrease in CD3+ γδ and CD3+CD8+ γδ T cells in peripheral blood of patients with CC vs. healthy subjects (p < 0.001)
Apoptosis was significantly increased in all conventional T lymphocytes and both αβ and γδ T cell subsets in patients with CC vs healthy subjects (Fig 3)
Summary
Colorectal cancer (CRC) is the fourth most common cancer and the third cause of cancerrelated death worldwide [1]. Alterations on the immunosurveillance system have been pointed as critical on CRC progression and prognosis [2,3]. Murine experiments showed that γδ T cells were the first group of T cells recruited into tumor injection site [7,8]. This cytokine is necessary in the protective responses against tumor development, its concentration may not be an indicative parameter of tumor response because both NK, NKT and gamma delta T cells might provide the early source of this cytokine [9,10]. IL-22 produced by γδ T cells is a supervisor of the DNA damage response against environmental genotoxic factors in intestinal epithelial stem cells avoiding malignant transformation and cancer development [11]
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