Publications by authors named "Kathleen Ducoin"

While immune checkpoint (IC) therapies, particularly those targeting the PD-1/PD-L1 axis, have revolutionized the treatment of melanoma and several other cancers, their effect remains very limited in colorectal cancer (CRC). To define a comprehensive landscape of ICs in the human CRC tumor microenvironment (TME), we evaluated, using multiparametric flow cytometry, their ex vivo expression via tumor-infiltrating lymphocytes (TILs) (n = 40 CRCs) as well as that of their respective ligands on tumor and myeloid cells (n = 29). Supervised flow cytometry analyses showed that (i) most CD3 TILs expressed PD-1 and TIGIT and, to a lesser extent, Tim-3, Lag3 and NKG2A, and (ii) EpCAM tumor cells and CD11b myeloid cells differed in their IC ligand expression profile, with a strikingly high expression of CD155 by tumor cells.

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Recently, the inhibitory CD94/NKG2A receptor has joined the group of immune checkpoints (ICs) and its expression has been documented in NK cells and CD8 T lymphocytes in several cancers and some infectious diseases. In colorectal cancer (CRC), we previously reported that NKG2A tumor-infiltrating lymphocytes (TILs) are predominantly CD8 αβ T cells and that CD94 overexpression and/or its ligand HLA-E were associated with a poor prognosis. This study aimed to thoroughly characterize the NKG2A CD8 TIL subpopulation and document the impact of NKG2A on anti-tumor responses in CRC.

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The 24th edition of the annual NAT conference (Nantes Actualités Transplantation) and the 4th edition of the biennial LabEx IGO meeting (Immunotherapy Graft Oncology) were held jointly around a common theme: "New horizons in immunotherapy", on May 31st and June 1st 2021 to highlight new findings in the fields of transplantation, autoimmunity and cancer.

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Article Synopsis
  • * The inflammasome pathway, particularly through the action of caspase-1 and its role in maturing IL-18, could play a crucial role in boosting T-helper/cytotoxic immune responses against tumors.
  • * Analysis of CRC patient cohorts indicates that many tumor cells have an active caspase-1/IL-18 pathway, which is associated with TIL density and microsatellite status, suggesting that targeting this pathway may amplify the anti-tumor immune response in certain CRC groups.
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We previously demonstrated that HLA-E/β2m overexpression by tumor cells in colorectal cancers is associated with an unfavorable prognosis. However, the expression of its specific receptor CD94/NKG2 by intraepithelial tumor-infiltrating lymphocytes, their exact phenotype and function, as well as the relation with the molecular status of colorectal cancer and prognosis remain unknown. Based on a retrospective cohort of 234 colorectal cancer patients, we assessed the expression of HLA-E, β2m, CD94, CD8, and NKp46 by immunohistochemistry on tissue microarray.

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