한빛사 논문
Yeon Hee Park1,7,8,*, Samir Lal2,7, Jeong Eon Lee1,7, Yoon-La Choi1,7, Ji Wen2, Sripad Ram3, Ying Ding2, Soo-Hyeon Lee4, Eric Powell2, Se Kyung Lee1, Jong Han Yu1, Keith A. Ching2, Jae-Yong Nam1, Seok Won Kim1, Seok Jin Nam1, Ji-Yeon Kim1, Soo Youn Cho1, Seri Park1, Jinho Kim5, Soohyn Hwang1, Yu Jin Kim1, Vinicius Bonato6, Diane Fernandez2, Shibing Deng6, Shuoguo Wang2, Hyuntae Shin5, Eun-Suk Kang1, Woong-Yang Park5, Paul A. Rejto2, Jadwiga Bienkowska2 & Zhengyan Kan2,8,*
1 Samsung Medical Center, Seoul, Korea.
2 Oncology Research & Development, Pfizer, San Diego, CA, USA.
3 Drug Safety R&D, Pfizer, San Diego, CA, USA.
4 Pfizer Oncology, Seoul, Korea.
5 Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
6 Biostatistics, Pfizer, San Diego, CA, USA.
7 These authors contributed equally: Yeon Hee Park, Samir Lal, Jeong Eon Lee, Yoon-La Choi.
8 These authors jointly supervised this work: Yeon Hee Park, Zhengyan Kan.
*Corresponding author
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.
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