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Mucosa-associated invariant T cells infiltrate hepatic metastases in patients with colorectal carcinoma but are rendered dysfunctional within and adjacent to tumor microenvironment


Mucosa-associated invariant T (MAIT) cells are innate-like T lymphocytes that are unusually abundant in the human liver, a common site of colorectal carcinoma (CRC) metastasis. However, whether they contribute to immune surveillance against colorectal liver metastasis (CRLM) is essentially unexplored. In addition, whether MAIT cell functions can be impacted by chemotherapy is unclear. These are important questions given MAIT cells’ potent immunomodulatory and inflammatory properties. Herein, we examined the frequencies and functions of peripheral blood, healthy liver tissue, tumor-margin and tumor-infiltrating MAIT cells in 21 CRLM patients who received no chemotherapy, FOLFOX, or a combination of FOLFOX and Avastin before they underwent liver resection. We found that MAIT cells, defined as CD3ε+Vα7.2+CD161++ or CD3ε+MR1 tetramer+ cells, were present within both healthy and tumor-afflicted hepatic tissues. Paired and grouped analyses of samples revealed the physical proximity of MAIT cells to metastatic lesions to drastically influence their functional competence. Accordingly, unlike those residing in the healthy liver compartment, tumor-infiltrating MAIT cells failed to produce IFN-γ in response to a panel of TCR and cytokine receptor ligands, and tumor-margin MAIT cells were only partially active. Furthermore, chemotherapy did not account for intratumoral MAIT cell insufficiencies. Our findings demonstrate for the first time that CRLM-penetrating MAIT cells exhibit wide-ranging functional impairments, which are dictated by their physical location but not by preoperative chemotherapy. Therefore, we propose that MAIT cells may provide an attractive therapeutic target in CRC and that their ligands may be combined with chemotherapeutic agents to treat CRLM.

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ATP-binding cassette subfamily B member 1


American Society of Anesthesiologists


Colorectal carcinoma


Colorectal liver metastasis


Eastern cooperative oncology group


Leucovorin calcium (folinic acid)/5-fluorouracil/oxaliplatin




Granzyme B


Hepatic [non-parenchymal] mononuclear cells


Mucosa-associated invariant T [cell]


Multi-drug resistance protein 1


[non-parenchymal] mononuclear cells


MHC-related protein 1


Natural-killer group 2, member D


Natural killer T [cell]




Recombinant [human] interleukin


Staphylococcal enterotoxin B


T helper 1


T helper 17


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This work was funded by a Canadian Institutes of Health Research (CIHR) operating Grant (MOP-130465) to S.M. Mansour Haeryfar and by a Dean’s Research Initiative Award from Schulich School of Medicine and Dentistry, Western University, to Roberto Hernandez-Alejandro and S.M. Mansour Haeryfar. Khashayarsha Khazaie is supported by grant R01CA160436 from NIH, and Christopher R. Shaler is a CIHR postdoctoral fellowship recipient. We thank members of the Haeryfar laboratory for helpful discussions, Delfina Mazzuca for production and purification of staphylococcal enterotoxin B, and Katie Bain for technical assistance with preparation of Klebsiella lysate.

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Shaler, C.R., Tun-Abraham, M.E., Skaro, A.I. et al. Mucosa-associated invariant T cells infiltrate hepatic metastases in patients with colorectal carcinoma but are rendered dysfunctional within and adjacent to tumor microenvironment. Cancer Immunol Immunother 66, 1563–1575 (2017).

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  • MAIT cells
  • Colon cancer
  • Liver metastasis
  • Tumor-infiltrating lymphocytes
  • Immune surveillance
  • Chemotherapy