Deep immune profiling of ovarian tumors identifies minimal MHC-I expression after neoadjuvant chemotherapy as negatively associated with T-cell-dependent outcome

Autor: Kim L. Brunekreeft, Sterre T. Paijens, Maartje C.A. Wouters, Fenne L. Komdeur, Florine A. Eggink, Joyce M. Lubbers, Hagma H. Workel, Elisabeth C. Van Der Slikke, Noor E.J. Pröpper, Ninke Leffers, Julien Adam, Harry Pijper, Annechien Plat, Arjan Kol, Hans W. Nijman, Marco De Bruyn
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: OncoImmunology, Vol 9, Iss 1 (2020)
Druh dokumentu: article
ISSN: 2162-402X
2162402X
DOI: 10.1080/2162402X.2020.1760705
Popis: Epithelial Ovarian cancer (EOC) is the most lethal gynecological malignancy and has limited curative therapeutic options. Immunotherapy for EOC is promising, but clinical efficacy remains restricted to a small percentage of patients. Several lines of evidence suggest that the low response rate might be improved by combining immunotherapy with carboplatin and paclitaxel, the standard-of-care chemotherapy for EOC. Here, we assessed the immune contexture of EOC tumors, draining lymph nodes, and peripheral blood mononuclear cells during carboplatin/paclitaxel chemotherapy. We observed that the immune contexture of EOC patients is defined by the tissue of origin, independent of exposure to chemotherapy. Summarized, draining lymph nodes were characterized by a quiescent microenvironment composed of mostly non-proliferating naïve CD4 + T cells. Circulating T cells shared phenotypic features of both lymph nodes and tumor-infiltrating immune cells. Immunologically ‘hot’ ovarian tumors were characterized by ICOS, GITR, and PD-1 expression on CD4 + and CD8 + cells, independent of chemotherapy. The presence of PD-1 + cells in tumors prior to, but not after, chemotherapy was associated with disease-specific survival (DSS). Accordingly, we observed high MHC-I expression in tumors prior to chemotherapy, but minimal MHC-I expression in tumors after neoadjuvant chemotherapy, even though there were no differences in the number of tumor-infiltrating lymphocytes (TIL) in both groups. We therefore speculate that the TIL influx into the chemotherapy tumor microenvironment may be a consequence of the general inflammatory nature of chemotherapy-experienced tumors. Strategies to upregulate MHC-I during or after neoadjuvant chemotherapy may thus improve treatment outcome in these patients.
Databáze: Directory of Open Access Journals
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