Tumor-Infiltrating Cytotoxic T Cells and Tumor-Associated Macrophages Correlate With the Outcomes of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer

Frontiers in Oncology

Peiqiu Li¹  Qingling Zhang³  Yuqin Yang⁴  Hong Zhao⁴  Xiaohua Gong⁴  Liqian Su⁵  Wenjing Tian⁶  Lu Shi⁶  Bin Zhao⁷ 

[1] Department of Nephrology, The Fifth Hospital Affifiliated of Sun Yat-sen University, Zhuhai, China;Department of Pathology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China;Department of Pathology, School of Basic Medical Science, Southern Medical University, Guangzhou, China;Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China;Precision Medicine Center of Harbin Medical University Cancer Hospital, Harbin, China;The Cancer Center of The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, China;The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China;

关键词: cytotoxic T lymphocytes;    tumor-associated macrophages;    rectal cancer;    neoadjuvant chemoradiotherapy;    pathological complete response;   

DOI  :  10.3389/fonc.2021.743540

来源: DOAJ

【 摘 要 】

BackgroundTumor-infiltrating immune cells (TIICs) play a key role in immunoregulatory networks and are related to tumor development. Emerging evidence shows that these cells are associated with sensitivity to chemotherapy and radiotherapy. However, the predictive role of TIICs in the outcomes of neoadjuvant chemoradiotherapy (nCRT) for locally advanced rectal cancer (LARC) is unclear.MethodsImaging mass cytometry (IMC) was performed to comprehensively assess the immune status before nCRT in 6 patients with LARC (3 achieved pathological complete response (pCR), 3 did not) with matched clinicopathological parameters. Immunohistochemistry (IHC) for CD8, CD163 and Foxp3 on biopsy samples from 70 patients prior to nCRT and logistic regression analysis were combined to further evaluate its predictive value for treatment responses in an independent validation group.ResultsA trend of increased CD8+ cytotoxic T lymphocytes (CTLs) and decreased CD163+ tumor-associated macrophages (TAMs) and Foxp3+ regulatory T cells (Tregs) in the pCR group was revealed by IMC. In the validation group, CTLs and TAMs were strong predictors of the clinical response to nCRT. High levels of CTLs were positively associated with the pCR ratio (OR=1.042; 95% CI: 1.015~1.070, p=0.002), whereas TAMs were correlated with a poor response (OR=0.969; 95% CI: 0.941~0.998, p=0.036). A high density of TAMs was also associated with an advanced cN stage.ConclusionCTLs in the tumor microenvironment (TME) may improve the response to nCRT, whereas TAMs have the opposite effect. These results suggest that these cells might be potential markers for the clinical outcomes of nCRT and aid in the clinical decision-making of LARC for improved clinical outcomes.

【 授权许可】

Unknown