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  • TNFR2+ TILs are significant...
    Dadiani, Maya; Necula, Daniela; Kahana-Edwin, Smadar; Oren, Nino; Baram, Tamir; Marin, Irina; Morzaev-Sulzbach, Dana; Pavlovski, Anya; Balint-Lahat, Nora; Anafi, Liat; Wiemann, Stefan; Korner, Cindy; Gal-Yam, Einav Nili; Avivi, Camila; Kaufman, Bella; Barshack, Iris; Ben-Baruch, Adit

    Cancer Immunology, Immunotherapy, 07/2020, Letnik: 69, Številka: 7
    Journal Article

    In view of the relatively limited efficacy of immunotherapies targeting the PD-1–PD-L1 axis in triple-negative breast cancer (TNBC) and of published reports on tumor-promoting roles of TNFR2+ tumor-infiltrating lymphocytes (TNFR2+ TILs), we determined the incidence of TNFR2+ TILs in TNBC patient tumors, their association with disease outcome and relations with PD-1+ TILs. Using a cohort of treatment-naïve TNBC patients with long follow-up ( n  = 70), we determined the presence of TNFR2+ TILs and PD-1+ TILs by immunohistochemistry. TILs (≥ 1% of cellular mass) and TNFR2+ TILs (≥ 1% of total TILs) were detected in 96% and 74% of tumors, respectively. The presence of TILs at > 5% of tumor cell mass (“Positive TILs”), as well as of positive TNFR2+ TILs (> 5%), was independently associated with good prognosis, and combination of both parameters demonstrated superior outcome relative to their lower levels. PD1+ TILs (> 5/hot spot) were detected in 63% of patients. High levels of PD-1+ TILs (> 20/hot spot) showed an unfavorable disease outcome, and in their presence, the favorable outcome of positive TNFR2+ TILs was ablated. Thus, TNFR2+ TILs are strongly connected to improved prognosis in TNBC; these findings suggest that TNFR2+ TILs have favorable effects in TNBC patients, unlike the tumor-promoting roles attributed to them in other cancer systems. Overall, our observations propose that the TNFR2+ TIL subset should not be targeted in the course of TNBC therapy; rather, its beneficial impacts may become into power when anti-PD-1 regimens—that may potentiate immune activities—are administered to TNBC patients.