Relationship between peripheral blood lymphocyte subsets and neoadjuvant therapy efficacy in patients with colorectal cancer
Objective To investigate the impact of neoadjuvant therapy on the absolute counts and percentages of peripheral blood lymphocyte subsets in rectal cancerpatientsand examine the relationship between the efficacy of neoadjuvant therapy and lymphocyte subsets.Methods A retrospective analysis was conducted on locally advanced rectal cancer patients treated at Fudan University Shanghai Cancer Center from January 1,2020 to December 31,2023.All enrolled patients received preoperative neoadjuvant therapy[short-course radiotherapy followed by four cycles of PD-1(programmed cell death protein 1)monoclonal antibody combined with Xelox chemotherapy].Flow cytometry was used before and after neoadjuvant therapy to assess the absolute counts and percentages of peripheral blood lymphocyte subsets,including CD3+T cells,CD4+T cells,CD8+T cells,B cells,NK cells,as well as the percentage of CD4+CD25+CD127low regulatory T cells within CD4+T cells(CD4+Treg%)and the percentage offunctional CD8+T cells withintotalTcells(CD8+CD28+T%).Based on these criteria,58 patients were eligible for the study.Following neoadjuvant therapy,therapeutic efficacy was evaluated through clinical and pathological diagnosis,classifying patients intoa complete response(CR)group(including clinical complete response and pathologic complete response)and non-CR group.The CR group consisted of 20males and 7 females(mean age 52.89±9.95 years),while the non-CR group included 17males and 14 females(mean age 57.26±11.05 years).Paired t-test were used to compare changes in lymphocyte subsets before and after neoadjuvant therapy,and independent two-sample-t-tests were applied to analyze the differences in post-treatment changes and the basal levels of lymphocyte subsets between CR group and non-CR group.Receiver operating characteristic(ROC)curve were employed to evaluate the predictive performance of baseline lymphocyte subsets for the efficacy of neoadjuvant therapy in rectal cancer patients.A validation cohort(n=104)with only baseline lymphocyte subset data was used to assess the coincidence of the predictive indicators.Results After completion of neoadjuvant therapy,all patients showed a reduction in the absolute counts of CD3+T,CD4+T,CD8+T,B and NK cells(P<0.05),with an increase in CD8+T%and NK%(P<0.05),and a decrease in B%(P<0.05).No statistically significant differences were observed in CD3+T%,CD4+T%,CD4+Treg%and CD8+CD28+T%.These changes were independent of therapeutic efficacy,however,baseline levels of CD3+T,CD4+T,CD8+T absolute counts,as well as CD3+T%,CD8+T%and CD8+CD28+T%,were significantly higher in the CR group than in the non-CR group(P<0.05).ROC curve analysis of these efficacy-related baseline indicators showed areas under the curve(AUC)of 0.838,0.756,0.839,0.659,0.702 and 0.858,respectively.Combining CD3+T absolute count with CD8+CD28+T%yielded an AUC of 0.886,with a sensitivity of 81.5%and specificity of 90.3%.In the validation cohort,the positive predictive consistency for these indicators ranged 69.4%to 97.5%,while negative predictive consistency ranged from 69.8%to 84.4%.Conclusions Neoadjuvant therapy for rectal cancer affects the ratio of lymphocytes,elevates the proportion of immune cells with anti-tumor effects.The number and ratio of lymphocyte subsets before treatment can predict the efficacy of neoadjuvant therapy for rectal cancer.