Correlation Between Baseline Lymphocyte Subsets Count In Peripheral Blood And The Efficacy Of Anti-PD-1 Therapy In Patients With Malignant Melanoma

Background and ObjectiveMalignant tumor has become a common disease with high mortality rate,which seriously threatens human physical and mental health and causes severe burden to the world and China’s socioeconomy.As a kind of tumor with little incidence but high malignancy,melanoma tends to occur in middle and old aged people,is highly aggressive and proliferative,and has a poor prognosis,its average survival after developing distant metastasis is only 6-9 months,and its 5-year survival rate is less than 5%.Conventional treatments for malignant melanoma are unsatisfactory,the advent and development of immunotherapy have resulted in significant improvements in overall survival for patients with malignant melanoma,particularly the advent of immune checkpoint inhibitors has driven the development of immunotherapy for melanoma.Although immunotherapy benefits cancer patients,it also faces many unprecedented challenges,such as the low overall efficiency of immunotherapy,some patients show pseudo progress,delayed response and so on.Therefore,the prediction of the efficacy of immunotherapy can help screen out the suitable population and make them better benefit from it.The occurrence,development and prognosis of tumor are closely related to the immune system of human body.Therefore,as an important cellular component of immune response function,lymphocyte is closely related to tumor immunity.Some studies have proved that each subgroup of lymphocyte plays a dual role in tumor immunity,and the stability of lymphocyte count in human peripheral blood is high,which can be easily detected.Therefore,the immune status of patients can be reflected based on the level of peripheral lymphocytes.In this context,through the detection and analysis of peripheral lymphocyte indexes in patients with melanoma treated with PD-1 antibody,we can judge the correlation between PD-1 antibody and the short-term curative effect and clinical symptoms of patients,and determine the convenient and efficient therapeutic markers,so as to provide support for the prognosis analysis of such patients.MethodsForty patients with stage Ⅳ malignant melanoma who were admitted to the Immunotherapy Department of the Affiliated Cancer Hospital of Zhengzhou University on January 1,2018 and received PD-1 antibody therapy were analyzed.The basic data of the patients were collected,including gender,age,smoking history,tumor type and tumor location.The peripheral blood of the patients before treatment was collected and the baseline lymphoid immune cell index was detected.The imaging data,including MRI,CT and ultrasound,were collected at the same time.All patients received PD-1 antibody treatment for at least 12 weeks.The cut-off values of total lymphocyte absolute count,T lymphocyte absolute count,B lymphocyte absolute count and Treg cell proportion were determined and divided into high and low levels.The survival status of patients was analyzed by K-M method,and the rank sum test was performed.The influencing factors of PD-1 antibody treatment efficacy were analyzed based on Cox regression model.The significant difference threshold was set to 0.05.ResultsThe best cutoff value of total lymphocyte absolute count was determined by the working characteristics(ROC)curve and area under curve(AUC)of subjects 1450.5/μl.The best cutoff value of T-lymphocyte absolute count 1085/μl.The best cutoff value of B lymphocyte absolute count 222.5/μl.The best cut-off value of Treg cell ratio was 9.2%.After statistical analysis,it was found that absolute count of total lymphocyte(P=0.031),absolute T-lymphocyte count(P=0.044),absolute B-lymphocyte count(P=0.024),Treg lymphocyte ratio(P=0.007)were significantly correlated with PFS in the non progressive survival period,but they could not be independent prognostic factors of PFS.The absolute count of total lymphocyte(P=0.044),absolute T-lymphocyte count(P=0.008),B-lymphocyte absolute count(P=0.002),Treg lymphocyte ratio(P=0.002)were significantly correlated with OS in the total survival period of patients.The significant variables of single factor analysis were included in multivariate analysis,and the independent prognostic factors(P=0.037)of Treg lymphocyte ratio were found.ConclusionsAt baseline,high total lymphocyte count,high T lymphocyte count,low B lymphocyte count and low proportion of Treg cells in peripheral blood were associated with good efficacy of PD-1 antibody treatment for malignant melanoma.Multivariate analysis showed that the proportion of Treg cells could be used as an independent predictor of OS.