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

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 and Zhengyan Kan ()
Additional contact information
Yeon Hee Park: Samsung Medical Center
Samir Lal: Oncology Research & Development, Pfizer
Jeong Eon Lee: Samsung Medical Center
Yoon-La Choi: Samsung Medical Center
Ji Wen: Oncology Research & Development, Pfizer
Sripad Ram: Drug Safety R&D, Pfizer
Ying Ding: Oncology Research & Development, Pfizer
Soo-Hyeon Lee: Pfizer Oncology
Eric Powell: Oncology Research & Development, Pfizer
Se Kyung Lee: Samsung Medical Center
Jong Han Yu: Samsung Medical Center
Keith A. Ching: Oncology Research & Development, Pfizer
Jae-Yong Nam: Samsung Medical Center
Seok Won Kim: Samsung Medical Center
Seok Jin Nam: Samsung Medical Center
Ji-Yeon Kim: Samsung Medical Center
Soo Youn Cho: Samsung Medical Center
Seri Park: Samsung Medical Center
Jinho Kim: Samsung Genome Institute, Samsung Medical Center
Soohyn Hwang: Samsung Medical Center
Yu Jin Kim: Samsung Medical Center
Vinicius Bonato: Biostatistics, Pfizer
Diane Fernandez: Oncology Research & Development, Pfizer
Shibing Deng: Biostatistics, Pfizer
Shuoguo Wang: Oncology Research & Development, Pfizer
Hyuntae Shin: Samsung Genome Institute, Samsung Medical Center
Eun-Suk Kang: Samsung Medical Center
Woong-Yang Park: Samsung Genome Institute, Samsung Medical Center
Paul A. Rejto: Oncology Research & Development, Pfizer
Jadwiga Bienkowska: Oncology Research & Development, Pfizer
Zhengyan Kan: Oncology Research & Development, Pfizer

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-19933-0

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