| Objective:To evaluate the clinical efficacy and safety of neoadjuvant chemotherapy(paclitaxel+platinum)and PD-1 antibody combined with neoadjuvant chemotherapy(paclitaxel+platinum)for locally advanced cervical cancer.At the same time,immunohistochemical techniques were used to analyze the changes of 11 immune indexes in paired tumor tissue samples before and after neoadjuvant therapy,so as to evaluate the impact of neoadjuvant therapy on tumor immune microenvironment.Methods:Patients diagnosed with cervical cancer and admitted to the First Affiliated Hospital of Nanchang University from October 2017 to October 2022 were collected.Cervical cancer patients receiving neoadjuvant chemotherapy(paclitaxel+platinum)or PD-1 antibody combined with neoadjuvant chemotherapy(paclitaxel+platinum+PD-1 antibody)were screened out,and cervical cancer patients receiving neoadjuvant chemotherapy(paclitaxel+platinum)were set as group A,and those receiving PD-1antibody combined with neoadjuvant chemotherapy(paclitaxel+platinum+PD-1antibody)were set as group B.After a prescribed course of neoadjuvant therapy,the patient was evaluated for radical hysterectomy by two experienced clinicians.General clinical data of patients who could undergo radical hysterectomy were collected,and patients with incomplete clinical data were excluded to determine the final number of patients enrolled.General clinical data before and after neoadjuvant therapy,perioperative data,surgical complications and drug-related adverse reactions were analyzed.At the same time,paired tumor tissue samples of patients undergoing biopsy before treatment and radical resection of cervical cancer were collected in this hospital.Immunohistochemical technology was used to explore the expression of cervical local immune components and tumor components before and after neoadjuvant therapy in cervical cancer patients,and statistical analysis was made of the influence of neoadjuvant therapy on tumor immune microenvironment.Results:1.In the neoadjuvant chemotherapy(paclitaxel+platinum)group,a total of 378patients with cervical cancer received radical hysterectomy after neoadjuvant chemotherapy in 258 patients.In the group of PD-1 antibody combined with neoadjuvant chemotherapy(paclitaxel+platinum+PD-1 antibody),a total of 44patients with cervical cancer received radical hysterectomy after neoadjuvant chemotherapy in 36 of them.Excluding patients with incomplete clinical data,54patients in the neoadjuvant chemotherapy(paclitaxel+platinum)group(Group A)and 31 patients in the PD-1 antibody combined with neoadjuvant chemotherapy(paclitaxel+platinum+PD-1 antibody)group(Group B)were finally included.A total of 15 paired specimens were collected from group A before and after treatment,and 9 paired specimens from group B before and after treatment.2.The clinical characteristics of patients were analyzed.The median age of patients in group A and group B was 56 years old and 53 years old respectively.According to FIGO 2018 staging,the staging ratio of patients in group A was 3(6%)in stage IB2,4(7%)in stage IB3,14(26%)in stage IIA1,12(22%)in stage IIA2,0in stage IIB,6(11%)in stage IIIA and 15(28%)in stage IIIC1p;The staging ratio of patients in group B was 5(16%)in stage IB2,6(19%)in stage IB3,2(6%)in stage IIA1,7(23%)in stage IIA2,2(7%)in stage IIB,1(3%)in stage IIIA,and 8(26%)in stage IIIC1p.The proportion of pathological tissue types in group A were 50(93%)squamous cell carcinoma and 4(7%)adenocarcinoma.The proportions of pathological tissue types in group B were 28(90%)squamous cell carcinoma,1(3%)adenocarcinoma and 2(7%)adeno-squamous cell carcinoma.The proportion of preoperative treatment cycles in group A was 4(7%)in 1 cycle,44(82%)in 2 cycles,5(9%)in 3 cycles,and 1(2%)in 4 cycles.The number of preoperative treatment cycles in group B was 27(87%)in 2 cycles and 4(13%)in 3 cycles.The median time between the first neoadjuvant treatment to surgery was 49 days in both groups.The mean days of post-surgery hospitalization in group A and group B were 9.37±2.85days and 8.03±2.79 days,P<0.05.No 30-day unscheduled admission patients were found in both groups.3.According to the analysis of clinical data,the mean tumor volumes of group A before and after treatment were 23.56±19.49cm~3and 9.19±12.97cm~3,P<0.001;The mean tumor volume of group B before and after treatment were 38.94±50.94cm~3and4.75±7.38cm~3,P<0.001.Complete response(CR)was achieved in 11(20%)patients in group A and 15(48%)patients in group B,P<0.05;Partial response(PR)was achieved in 25(46%)patients in group A and 10(32%)patients in group B,P=0.255;Progressive disease(PD)was observed in 2(4%)patients in group A and 1(3%)patients in group B,P=1.000;Stable disease(SD)was observed in 16(30%)patients in group A and 5(16%)patients in group B,P=0.199.The mean values of serum squamous cell carcinoma associated antigen(SCC-Ag)in group A before and after treatment were 12.23±14.01 ng/ml and 4.25±5.34 ng/ml,P<0.001;The mean values of serum SCC-Ag in group B before and after treatment were 29.30±34.22 ng/ml and3.76±5.96 ng/ml,respectively,P<0.001.4.Analysis of perioperative data showed that the mean operation time of group A and group B was 235±62.05min and 223±58.57min,respectively,P=0.491.The mean intraoperative blood loss of group A and group B was 340.19±342.93ml and383.23±288.71ml,P=0.236.In group A and group B,12(22%)and 2(6%)patients with intraoperative and postoperative ureteral stents were implanted,respectively,P=0.073.Analysis of postoperative pathological results showed that there were 6(11%)and 0 patients with positive incisal margins in group A and Group B,P=0.082.There were 20(37%)patients in group A and 8(26%)patients in group B with positive lymph nodes,P=0.343.Pathological complete response(p CR)was achieved in 1(2%)and 4(13%)patients in group A and Group B,respectively,P=0.057.5.Analysis of related adverse reactions,general adverse reactions mainly include anemia,leukopenia,thrombocytopenia,kidney injury,liver injury,hypoproteinemia,hypocalcemia,hypokalemia and hyponatremia.There were 27(50%)and 17(55%)cases of anemia in group A and Group B,P<0.05;There was no statistical difference in other general adverse reactions.Immune-related adverse reactions include rash,pruritus,vitiligo,diarrhea,mouth ulcers,dyspnea,cough,and fecal occulted blood.In group B,2 patients showed pruritus,4 patients showed weak positive fecal occult blood,and other immune-related adverse reactions did not occur.6.The changes of tumor immune microenvironment before and after treatment were analyzed.After treatment,the expressions of CD4,CD8,CD20,CD11c,CD68and PD-1 in the tumor immune microenvironment increased in both groups,while the expressions of Fox P3,IDO-1,PD-L1,P16 and CK decreased.In group A,the expression of CD4 was higher,and the expression of Fox P3 and PD-L1 was lower after treatment.After treatment,the expressions of CD8,CD20,CD11c,CD68 and PD-1 were higher in group B,while the expression of IDO-1 was lower.Conclusion:Compared with neoadjuvant chemotherapy alone(paclitaxel+platinum),PD-1antibody combined with neoadjuvant chemotherapy(paclitaxel+platinum+PD-1antibody)can more effectively reduce the mass volume and serum SCC-Ag,improve the resection rate,and reduce the incidence of positive incisal margin and residual lesions.At the same time,the injury of ureter during operation is reduced,and the probability of intraoperative and postoperative placement of ureteral stent is reduced.Neoadjuvant chemotherapy combined with PD-1 antibody did not significantly increase the incidence of adverse reactions in patients.Neoadjuvant therapy reshaped the immune microenvironment of cervical cancer.After neoadjuvant therapy,the expressions of CD4,CD8,CD20,CD11c,CD68 and PD-1 molecules in the tumor microenvironment increased,while the expressions of Fox P3,IDO-1,PD-L1,P16 and CK molecules were decreased in both groups.Compared with neoadjuvant chemotherapy alone(paclitaxel+platinoid),combined with PD-1 antibody can increase the expression of CD8,CD20,CD11c,CD68 and PD-1 molecules in tumor microenvironment,promote immune cell invasion and enhance the anti-tumor effect of the body. |
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