Journal Article

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

Lee, Soo-Hyeon, Ding, Ying, Nam, Jae-Yong, Kim, Seok Won, Park, Seri, Wang, Shuoguo, Shin, Hyuntae, Ching, Keith A., Kim, Ji-Yeon, Kim, Jinho, Bienkowska, Jadwiga, Rejto, Paul A., Fernandez, Diane, Powell, Eric, Cho, Soo Youn, Bonato, Vinicius, Park, Yeon Hee, Wen, Ji, Park, Woong-Yang, Kan, Zhengyan, Lee, Jeong Eon, Choi, Yoon-La, Kang, Eun-Suk, Yu, Jong Han, Hwang, Soohyn, Kim, Yu Jin, Ram, Sripad, Nam, Seok Jin, Deng, Shibing, Lal, Samir, Lee, Se Kyung

2020

Overview

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. Neoadjuvant chemotherapy is a therapeutic option for the treatment of breast cancer. Here, the authors characterize changes in the gene expression profiles and immune microenvironment in serial breast cancer biopsies taken before, during and after neoadjuvant chemotherapy.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 45 / 45/91 / 631/67/1059/99 / 631/67/1347 / 631/67/69 / Anthracyclines - therapeutic use / B7-H1 Antigen - antagonists & inhibitors / B7-H1 Antigen - genetics / B7-H1 Antigen - immunology / Biopsy / Breast cancer / Breast Neoplasms - drug therapy / Breast Neoplasms - genetics / Breast Neoplasms - immunology / Breast Neoplasms - mortality / Carcinoma, Ductal, Breast - drug therapy / Carcinoma, Ductal, Breast - genetics / Carcinoma, Ductal, Breast - immunology / Carcinoma, Ductal, Breast - mortality / CD8 antigen / CD8-Positive T-Lymphocytes - drug effects / CD8-Positive T-Lymphocytes - immunology / CD8-Positive T-Lymphocytes - pathology / Cell Cycle Proteins - genetics / Cell Cycle Proteins - immunology / Chemotherapy / Cyclophosphamide - therapeutic use / Cytotoxicity / Disease-Free Survival / Docetaxel - therapeutic use / Estrogen Receptor alpha - genetics / Estrogen Receptor alpha - immunology / Female / Gene expression / Gene Expression Profiling / Gene Expression Regulation, Neoplastic / Histopathology / Humanities and Social Sciences / Humans / Immune response / Immune system / Immunity, Innate / Inflammation / Interferon Regulatory Factors - genetics / Interferon Regulatory Factors - immunology / Longitudinal Studies / Lymphocytes / Lymphocytes T / Lymphocytes, Tumor-Infiltrating - drug effects / Lymphocytes, Tumor-Infiltrating - immunology / Lymphocytes, Tumor-Infiltrating - pathology / multidisciplinary / Neoadjuvant Therapy - methods / Neoplasm, Residual / PD-1 protein / Receptor, ErbB-2 - genetics / Receptor, ErbB-2 - immunology / Science / Science (multidisciplinary) / Surgery / Trastuzumab - therapeutic use / Treatment Outcome / Tumor Microenvironment - drug effects / Tumor Microenvironment - genetics / Tumor Microenvironment - immunology / Tumors