Significance Of Peripheral Blood Lymphocyte Subsets In Early Diagnosis Of Oligometastases In Patients With Rectal Cancer And Predictive Value Of The Subsets In Response To Neoadjuvant Therapy

Purpose:According to domestic and foreign guidelines,neoadjuvant chemoradiotherapy is the standard treatment for locally advanced rectal cancer as well as the resectable oligometastatic rectal cancer.However,ordinary imaging examine can not be fully and early identified for the oligomastases without clear pathological diagnosis.In the term of neoadjuvant therapy,the specificity of tumor markers and other clinical factors to predict tumor response is poor.The existing immune score is not applicable to rectal cancer patients who have received radiotherapy due to the destruction of tissue structure.In recent years,analysis of peripheral blood immune cell subsets has been considered as a potential method for preducting tumor response and prognosis.In this study,we aimed to predict oligometastatic and tumor responses for rectal cancer based on the analysis of peripheral blood immune cell subsets combined with the currently known clinical risk factors.A more individualized treatment plan would develop for different patients as far as possible.Methods:In this study,a total of 114 patients with locally advanced or oligometastatic rectal cancer from the Nanfang Hospital,Southern Medical University were retrospectively analyzed.The lymphocyte subsets were counted by flow cytometry before treatment,after radiotherapy and before surgery while the changes were observed.We also used univariate and multivariate Logistic regression analyses to find the independent predictor variables and developed a nomogram for oligometastasis of rectal cancer which was performed internal validation.At the same time,we also compared the effect of CD8+lymphocytes at three time points and their change ratio on the efficacy of neoadjuvant therapy,as well as the relationship with TILs(Tumor lymphocytes).Results:After concurrent chemoradiotherapy,there was significant lymphocyte decrease,which would recover before surgery gradually.It was still significantly lower than that before treatment.There was no significant change in the proportion of total T cells,the proportion of B cells decreased significantly,and the proportion of NK cells increased.The component proportion ratio of T cells changed significantly while the relative count of total T cells did not change.It showed that CD4+and CD45RA+decreased while CD8+and Treg increased,which caused the activation of T cells significantly.We developed a nomogram for predicting oligomastasis of rectal cancer by screening out CRM(Circumferential resection margin),CD4+/CD8+and globulin as risk factors through univariate and multivariate Logistic regression,which was performed the internal verification.The AUC(Area under curve)value was 0.813(0.703-0.923)in the training cohort and 0.799(0.603-0.996)in the validation cohort.The relative count of CD8+lymphocytes before treatment and the rate of change after neoadjuvant therapy were significantly different between the GR(Good response)group and the PR(Poor response)group.According to the cut-off values calculated by the Yorden index,94.7%(18/19)of the patients in the group with both low CD8+relative count before treatment and high rate of change had a good response,while there are only 54.3%(19/35)of the patients in the group with both high CD8+relative count and low rate of change.We also found that patients with lower relative count of CD8+lymphocytes in their peripheral blood had more local infiltration of CD8+lymphocytes before treatment.Conclusions:The lymphocyte count decreased significantly after concurrent chemoradiotherapy which resulted in the activation of cellular immunity.The immunosuppression was also stronger through the feedback regulation.Pre-treatment nomogram based on CRM,globulin,and CD4+/CD8+predict early oligometastases in locally advanced rectal cancer.At the same time,radiotherapy significantly activated the cellular immunity of the patients.Patients with lower absolute count of CD8+lymphocytes before treatment and higher rate of CD8+lymphocytes change after treatment were more likely to benefit from neoadjuvant therapy.The conclusions above can help physicians make more accurate diagnosis,predict the response of neoadjuvant therapy before treatment as well as provide a more individualized treatment plan for patients.