Background: Distant metastasis is the major cause of mortality in patients with locally advanced rectal cancer (LARC) following neoadjuvant chemoradiotherapy. Local radiotherapy can trigger an abscopal response to metastatic tumor cells. However, the abscopal effect is a rare event. CD4+ regulatory T (Treg) cell is a highly immune-suppressive subset which impedes immune surveillance against cancer, prevents the development of effective antitumor immunity and promotes tumor progression. We assume that the exploitation of the proimmunogenic effects of radiotherapy with anti-CD25 or anti-Cytotoxic T-Lymphocyte Associated Protein 4 (anti-CTLA4) monoclonal antibodies (mAbs) may enhance the local and abscopal effects in rectal cancer and improve the therapeutic outcome. Methods: mRNA expression profiling of 81 pretreatment biopsy samples from LARC patients who received neoadjuvant radiotherapy (nRT) was performed to analyze the correlation between gene expression and prognosis. A retrospective analysis of patients with rectal cancer with distant metastasis or synchronous extracolonic cancers was performed to evaluate the abscopal effect of radiotherapy on rectal cancer. Two different dual-tumor mouse models were established to investigate the efficacy of single dose and dose-fractionated radiotherapy combined with anti-CD25 or anti-CTLA4 and anti-Programmed cell death 1 ligand 1 (anti-PD1) mAbs on the local tumor growth and liver metastasis. The univariate Cox regression analysis, one-way analysis of variance, Dunnett's test, a mixed-effect linear model and Kaplan-Meier survival analysis were used to calculate p values. Results: The proportion of Tregs in pre-nRT biopsies was negatively correlated with prognosis (p=0.007). The retrospective analysis showed that regressing liver metastases were infiltrated by CD8+ T cells. In contrast, stable/progressing metastases and synchronous extracolonic cancers were characterized by PD1+ T cells and Tregs infiltration. Animal experiment results demonstrated that the combination of radiotherapy and anti-CD25/CTLA4 mAb resulted in a significant increase in CD8+ T cells and CD8+/CD4+ ratio in primary and secondary tumors compared with the irradiation alone group (all p<0.05 or p<0.01). The combined treatment was able to decrease Tregs, PD1+CD8+ and PD1+CD4+ T cells (p<0.05), suppress locally irradiated and distal unirradiated tumor growth, and improve overall survival rate. Radiotherapy in conjunction with anti-CTLA4 reduced liver metastasis (p<0.05). Conclusions: These data indicated that radiotherapy plus depletion of Tregs was able to improve the antitumor response and generate an abscopal effect.Keywords: gastrointestinal neoplasms; immunotherapy; radiotherapy; tumor microenvironment.

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乐备实（上海优宁维生物科技股份有限公司旗下全资子公司），是国内专注于提供高质量蛋白检测以及组学分析服务的实验服务专家，自2018年成立以来，乐备实不断寻求突破，公司的服务技术平台已扩展到单细胞测序、空间多组学、流式检测、超敏电化学发光、Luminex多因子检测、抗体芯片、PCR Array、ELISA、Elispot、PLA蛋白互作、多色免疫组化、DSP空间多组学等30多个，建立起了一套涵盖基因、蛋白、细胞以及组织水平实验的完整检测体系。

 
我们可提供从样本运输、储存管理、样本制备、样本检测到检测数据分析的全流程服务。凭借严格的实验室管理流程、标准化实验室操作、原始数据储存体系以及实验项目管理系统，已经为超过3000家客户单位提供服务，年检测样本超过100万，受到了广大客户的信任与支持。