TY - JOUR
T1 - Abundance of regulatory t cell (Treg) as a predictive biomarker for neoadjuvant chemotherapy in triple-negative breast cancer
AU - Oshi, Masanori
AU - Asaoka, Mariko
AU - Tokumaru, Yoshihisa
AU - Angarita, Fernando A.
AU - Yan, Li
AU - Matsuyama, Ryusei
AU - Zsiros, Emese
AU - Ishikawa, Takashi
AU - Endo, Itaru
AU - Takabe, Kazuaki
N1 - Funding Information:
Funding: This work was supported by the National Institutes of Health, USA grant R01CA160688; a grant from the Edward K. Duch Foundation to K.T.; Grant-in-Aid for Scientific Research Grant Numbers 19H03714 and 18K19576 to M.N.; and National Cancer Institute, USA cancer center support grant P30-CA016056 to Roswell Park Comprehensive Cancer Center (RPCCC).
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/10
Y1 - 2020/10
N2 - Regulatory CD4+ T cell (Treg), a subset of tumor-infiltrating lymphocytes (TILs), are known to suppress anticancer immunity but its clinical relevance in human breast cancer remains unclear. In this study, we estimated the relative abundance of Tregs in breast cancer of multiple patient cohorts by using the xCell algorithm on bulk tumor gene expression data. In total, 5177 breast cancer patients from five independent cohorts (TCGA-BRCA, GSE96058, GSE25066, GSE20194, and GSE110590) were analyzed. Treg abundance was not associated with cancer aggressiveness, patient survival, or immune activity markers, but it was lower in metastatic tumors when compared to matched primary tumors. Treg was associated with a high mutation rate of TP53 genes and copy number mutations as well as with increased tumor infiltration of M2 macrophages and decreased infiltration of T helper type 1 (Th1) cells. Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) was significantly associated with low Treg abundance in triple negative breast cancer (TNBC) but not in ER-positive/Her2-negative subtype. High Treg abundance was significantly associated with high tumor expression of multiple immune checkpoint inhibitor genes. In conclusion, Treg abundance may have potential as a predictive biomarker of pCR after NAC in TNBC.
AB - Regulatory CD4+ T cell (Treg), a subset of tumor-infiltrating lymphocytes (TILs), are known to suppress anticancer immunity but its clinical relevance in human breast cancer remains unclear. In this study, we estimated the relative abundance of Tregs in breast cancer of multiple patient cohorts by using the xCell algorithm on bulk tumor gene expression data. In total, 5177 breast cancer patients from five independent cohorts (TCGA-BRCA, GSE96058, GSE25066, GSE20194, and GSE110590) were analyzed. Treg abundance was not associated with cancer aggressiveness, patient survival, or immune activity markers, but it was lower in metastatic tumors when compared to matched primary tumors. Treg was associated with a high mutation rate of TP53 genes and copy number mutations as well as with increased tumor infiltration of M2 macrophages and decreased infiltration of T helper type 1 (Th1) cells. Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) was significantly associated with low Treg abundance in triple negative breast cancer (TNBC) but not in ER-positive/Her2-negative subtype. High Treg abundance was significantly associated with high tumor expression of multiple immune checkpoint inhibitor genes. In conclusion, Treg abundance may have potential as a predictive biomarker of pCR after NAC in TNBC.
KW - Biomarker
KW - Cytolytic activity
KW - Immune cell
KW - Regulatory T cells
KW - Survival analysis
KW - Triple negative breast cancer
KW - Tumor immune microenvironment
KW - Tumor-infiltrating lymphocyte
KW - XCell
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U2 - 10.3390/cancers12103038
DO - 10.3390/cancers12103038
M3 - Article
AN - SCOPUS:85093702407
VL - 12
SP - 1
EP - 16
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 10
M1 - 3038
ER -