TY - JOUR
T1 - Chemotherapy shifts the balance in favor of cd8+ tnfr2+ tils in triple-negative breast tumors
AU - Baram, Tamir
AU - Erlichman, Nofar
AU - Dadiani, Maya
AU - Balint-Lahat, Nora
AU - Pavlovski, Anya
AU - Meshel, Tsipi
AU - Morzaev-Sulzbach, Dana
AU - Gal-Yam, Einav Nili
AU - Barshack, Iris
AU - Ben-Baruch, Adit
N1 - Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/6
Y1 - 2021/6
N2 - Triple-negative breast cancer (TNBC) is primarily treated via chemotherapy; in parallel, efforts are made to introduce immunotherapies into TNBC treatment. CD4+ TNFR2+ lymphocytes were reported as Tregs that contribute to tumor progression. However, our published study indicated that TNFR2+ tumor-infiltrating lymphocytes (TNFR2+ TILs) were associated with improved survival in TNBC patient tumors. Based on our analyses of the contents of CD4+ and CD8+ TILs in TNBC patient tumors, in the current study, we determined the impact of chemotherapy on CD4+ and CD8+ TIL subsets in TNBC mouse tumors. We found that chemotherapy led to (1) a reduction in CD4+ TNFR2+ FOXP3+ TILs, indicating that chemotherapy decreased the content of CD4+ TNFR2+ Tregs, and (2) an elevation in CD8+ TNFR2+ and CD8+ TNFR2+ PD-1+ TILs; high levels of these two subsets were significantly associated with reduced tumor growth. In spleens of tumor-bearing mice, chemotherapy down-regulated CD4+ TNFR2+ FOXP3+ cells but the subset of CD8+ TNFR2+ PD-1+ was not present prior to chemotherapy and was not increased by the treatment. Thus, our data suggest that chemotherapy promotes the proportion of protective CD8+ TNFR2+ TILs and that, unlike other cancer types, therapeutic strategies directed against TNFR2 may be detrimental in TNBC.
AB - Triple-negative breast cancer (TNBC) is primarily treated via chemotherapy; in parallel, efforts are made to introduce immunotherapies into TNBC treatment. CD4+ TNFR2+ lymphocytes were reported as Tregs that contribute to tumor progression. However, our published study indicated that TNFR2+ tumor-infiltrating lymphocytes (TNFR2+ TILs) were associated with improved survival in TNBC patient tumors. Based on our analyses of the contents of CD4+ and CD8+ TILs in TNBC patient tumors, in the current study, we determined the impact of chemotherapy on CD4+ and CD8+ TIL subsets in TNBC mouse tumors. We found that chemotherapy led to (1) a reduction in CD4+ TNFR2+ FOXP3+ TILs, indicating that chemotherapy decreased the content of CD4+ TNFR2+ Tregs, and (2) an elevation in CD8+ TNFR2+ and CD8+ TNFR2+ PD-1+ TILs; high levels of these two subsets were significantly associated with reduced tumor growth. In spleens of tumor-bearing mice, chemotherapy down-regulated CD4+ TNFR2+ FOXP3+ cells but the subset of CD8+ TNFR2+ PD-1+ was not present prior to chemotherapy and was not increased by the treatment. Thus, our data suggest that chemotherapy promotes the proportion of protective CD8+ TNFR2+ TILs and that, unlike other cancer types, therapeutic strategies directed against TNFR2 may be detrimental in TNBC.
KW - CD4+ lymphocytes
KW - CD8+ lymphocytes
KW - Forkhead box P3 (FOXP3)
KW - Programmed cell death protein 1 (PD-1)
KW - Splenocytes
KW - Triple-negative breast cancer (TNBC)
KW - Tumor necrosis factor receptor 2 (TNFR2)
KW - Tumor necrosis factor α (TNFα)
KW - Tumor-infiltrating lymphocytes (TILs)
UR - http://www.scopus.com/inward/record.url?scp=85110402078&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/cells10061429
DO - https://doi.org/10.3390/cells10061429
M3 - مقالة
C2 - 34201054
SN - 2073-4409
VL - 10
JO - Cells
JF - Cells
IS - 6
M1 - 1429
ER -
