Chemotherapy induces dynamic immune responses in breast cancers that impact treatment outcome.

Abstract

To elucidate the effects of neoadjuvant chemotherapy (NAC), we conduct whole transcriptome profiling coupled with histopathology analyses of a longitudinal breast cancer cohort of 146 patients including 110 pairs of serial tumor biopsies collected before treatment, after the first cycle of treatment and at the time of surgery. Here, we show that cytotoxic chemotherapies induce dynamic changes in the tumor immune microenvironment that vary by subtype and pathologic response. Just one cycle of treatment induces an immune stimulatory microenvironment harboring more tumor infiltrating lymphocytes (TILs) and up-regulation of inflammatory signatures predictive of response to anti-PD1 therapies while residual tumors are immune suppressed at end-of-treatment compared to the baseline. Increases in TILs and CD8+ T cell proportions in response to NAC are independently associated with pathologic complete response. Further, on-treatment immune response is more predictive of treatment outcome than immune features in paired baseline samples although these are strongly correlated.

• Authors: Yeon Hee Park, Samir Lal, Jeong Eon Lee, Yoon-La Choi, Ji Wen, Sripad Ram, Ying Ding, Soo-Hyeon Lee, Eric Powell, Se Kyung Lee, Jong Han Yu, Keith A Ching, Jae-Yong Nam, Seok Won Kim, Seok Jin Nam, Ji-Yeon Kim, Soo Youn Cho, Seri Park, Jinho Kim, Soohyn Hwang, Yu Jin Kim, Vinicius Bonato, Diane Fernandez, Shibing Deng, Shuoguo Wang, Hyuntae Shin, Eun-Suk Kang, Woong-Yang Park, Paul A Rejto, Jadwiga Bienkowska, Zhengyan Kan
• Journal: Nature communications (Nat Commun) Vol. 11 Issue 1 Pg. 6175 (12 02 2020) ISSN: 2041-1723 [Electronic] England
• PMID: 33268821 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anthracyclines
• B7-H1 Antigen
• CD274 protein, human
• Cell Cycle Proteins
• ESR1 protein, human
• Estrogen Receptor alpha
• Interferon Regulatory Factors
• Docetaxel
• Cyclophosphamide
• ERBB2 protein, human
• Receptor, ErbB-2
• Trastuzumab

Topics

• Anthracyclines (therapeutic use)
• B7-H1 Antigen (antagonists & inhibitors, genetics, immunology)
• Breast Neoplasms (drug therapy, genetics, immunology, mortality)
• CD8-Positive T-Lymphocytes (drug effects, immunology, pathology)
• Carcinoma, Ductal, Breast (drug therapy, genetics, immunology, mortality)
• Cell Cycle Proteins (genetics, immunology)
• Cyclophosphamide (therapeutic use)
• Disease-Free Survival
• Docetaxel (therapeutic use)
• Estrogen Receptor alpha (genetics, immunology)
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Immunity, Innate
• Interferon Regulatory Factors (genetics, immunology)
• Longitudinal Studies
• Lymphocytes, Tumor-Infiltrating (drug effects, immunology, pathology)
• Neoadjuvant Therapy (methods)
• Neoplasm, Residual
• Receptor, ErbB-2 (genetics, immunology)
• Trastuzumab (therapeutic use)
• Treatment Outcome
• Tumor Microenvironment (drug effects, genetics, immunology)