TNFR2+ TILs are significantly associated with improved survival in triple-negative breast cancer patients.
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
/ analysis
Carcinoma, Ductal, Breast
/ immunology
Female
Follow-Up Studies
Humans
Lymphocytes, Tumor-Infiltrating
/ immunology
Middle Aged
Prognosis
Receptors, Tumor Necrosis Factor, Type II
/ metabolism
Retrospective Studies
Survival Rate
Triple Negative Breast Neoplasms
/ immunology
Programmed cell death protein 1 (PD-1)
Triple-negative breast cancer (TNBC)
Tumor necrosis factor receptor 2 (TNFR2)
Tumor-infiltrating lymphocytes (TILs)
Journal
Cancer immunology, immunotherapy : CII
ISSN: 1432-0851
Titre abrégé: Cancer Immunol Immunother
Pays: Germany
ID NLM: 8605732
Informations de publication
Date de publication:
Jul 2020
Jul 2020
Historique:
received:
12
12
2019
accepted:
10
03
2020
pubmed:
22
3
2020
medline:
1
7
2020
entrez:
22
3
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32198536
doi: 10.1007/s00262-020-02549-0
pii: 10.1007/s00262-020-02549-0
doi:
Substances chimiques
Biomarkers, Tumor
0
Receptors, Tumor Necrosis Factor, Type II
0
TNFRSF1B protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1315-1326Références
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