Characterization of the tumor microenvironment and identification of spatially predictive biomarkers associated with beneficial neoadjuvant chemoradiotherapy in locally advanced rectal cancer

Zhang, Shifen1,2,3,4; Li, Na5; Wang, Feifei1,2; Liu, Hailing6; Zhang, Yuhan5; Xiao, Jinyuan5; Qiu, Weihao1,2; Zhang, Ceng1,2; Fan, Xinjuan6; Qiu, Mingxin1,2; Li, Mingzhou1,2; Tang, Hongzhen5; Fan, Shiheng5; Wang, Jiaqian5; Luo, Haitao5; Li, Xiangzhao1,2; Lin, Jie1,2,7; Huang, Yan6; Liang, Li1,2,7

2023-11-01

10.1016/j.phrs.2023.106974

PHARMACOLOGICAL RESEARCH   影响因子和分区

1043-6618

1096-1186

Neoadjuvant chemoradiotherapy (nCRT) has become the standard treatment for patients with locally advanced rectal cancer (LARC). However, 20-40% of patients with LARC show little to no response to nCRT. Thus, comprehensively understanding the tumor microenvironment (TME), which might influence therapeutic efficacy, and identifying robust predictive biomarkers is urgently needed. Pre-treatment tumor biopsy specimens from patients with LARC were evaluated in detail through digital spatial profiling (DSP), public RNA sequencing datasets, and multiplex immunofluorescence (mIF). DSP analysis revealed distinct characteristics of the tumor stroma compared to the normal stroma and tumor compartments. We identified high levels of human leukocyte antigen-DR/major histocompatibility complex class II (HLA-DR/MHC-II) in the tumor compartment and B cells in the stroma as potential spatial predictors of nCRT efficacy in the Discovery cohort. Public datasets validated their predictive capacity for clinical outcomes. Using mIF in an independent nCRT cohort and/or the total cohort, we validated that a high density of HLA-DR/MHC-II+ cells in the tumor and CD20 + B cells in the stroma was associated with nCRT efficacy (all p <= 0.021). Spatial profiling successfully characterized the LARC TME and identified robust biomarkers with the potential to accurately predict nCRT response. These findings have important implications for individualized therapy.

Locally advanced rectal cancer Neoadjuvant chemoradiotherapy Tumor microenvironment Biomarkers Digital spatial profiling Multiplex immunofluorescence

SCI

英语

其他

National Key R & D Program of China[2021YFF1201004] ; National Natural Science Foundation of China["82273358","82003059"] ; China Postdoctoral Science Foundation["2019M652963","2020M682624"]

Pharmacology & Pharmacy

Pharmacology & Pharmacy

WOS:001111367100001

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD

PHARMACOLOGY & TOXICOLOGY

Web of Science

1.Southern Med Univ, Nanfang Hosp, Sch Basic Med Sci, Dept Pathol, Guangzhou 510515, Peoples R China
2.Guangdong Prov Key Lab Mol Tumor Pathol, Guangzhou 510515, Peoples R China
3.Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Dept Pathol, Shenzhen 518020, Peoples R China
4.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen 518020, Peoples R China
5.YuceBio Technol Co Ltd, Shenzhen Engn Ctr Translat Med Precis Canc Immunod, Shenzhen 518000, Peoples R China
6.Sun Yat Sen Univ, Affiliated Hosp 6, Dept Pathol, Guangzhou 510655, Peoples R China
7.Jinfeng Lab, Chongqing 401329, Peoples R China

Zhang, Shifen,Li, Na,Wang, Feifei,et al. Characterization of the tumor microenvironment and identification of spatially predictive biomarkers associated with beneficial neoadjuvant chemoradiotherapy in locally advanced rectal cancer[J]. PHARMACOLOGICAL RESEARCH,2023,197.

Zhang, Shifen.,Li, Na.,Wang, Feifei.,Liu, Hailing.,Zhang, Yuhan.,...&Liang, Li.(2023).Characterization of the tumor microenvironment and identification of spatially predictive biomarkers associated with beneficial neoadjuvant chemoradiotherapy in locally advanced rectal cancer.PHARMACOLOGICAL RESEARCH,197.

Zhang, Shifen,et al."Characterization of the tumor microenvironment and identification of spatially predictive biomarkers associated with beneficial neoadjuvant chemoradiotherapy in locally advanced rectal cancer".PHARMACOLOGICAL RESEARCH 197(2023).