Neoadjuvant Therapy With Immune Checkpoint Inhibitors Can Reduce The Risk Of Postoperative Recurrence Of Resectable NSCLC

Background and purposeImmune checkpoint inhibitor(ICI)neoadjuvant immunotherapy has become an effective treatment method for resectable NSCLC.It can bring about the decrease in tumor volume,thus improve the surgical opportunity of radical resection,reducing the postoperative recurrence and metastasis risk after surgery,and improving the prognosis of patients.However,there are relatively few studies on the continuous application of ICI after operation.In this study,the subcutaneous transplantation model of murine lung cancer was constructed,and the commonly used ICI — —programmed death receptor-1(PD-1)monoclonal antibody was selected to evaluate the efficacy of preoperative and postoperative neoadjuvant immunotherapy with ICI on resectable NSCLC.MethodsTo establish the subcutaneous transplantation model of murine lung cancer,20C57BL/6 female mice were selected,all aged 6～8 weeks.Lewis lung cancer cells(LLC)was injected into the left axillary part of mice in the form of subcutaneous inoculation.Twenty tumor mice were randomly divided into experimental group(EG)and control group(CG).From 7 days after inoculation,the EG was treated with tail vein injection of PD-1 monoclonal antibody every 2 days,and the CG was given normal saline in the same dose at the same frequency,with tumor volume measured before each injection.The subcutaneous transplanted tumor was removed on the 14 th day.The expressions of CD45 and Ki67 were examined in the two groups,and the IOD under microscope was analyzed and compared.Three days after operation,the EG continued to be injected into PD-1 monoclonal antibody regularly and the CG into normal saline.The 28 th day after operation,all these mice were killed and dissected with pathological specimens taken.After HE staining,Pathological evaluation was performed under microscope.ResultsThe EG were injected with PD-1 monoclonal antibody at 7 days after tumor seeding,the tumor’s volume was significantly different from the CG at 9th,11 th and13th days,the result is statistically significant(P<0.001).The CD45 positively expressed in the EG’s tumor tissue.It was significantly higher than that in the CG(P=0.009);Compared with the CG,the EG’s expression of Ki67 was significantly inhibited(P=0.001).28 days after operation,pathological evaluation showed that 60%of the mice in the EG reached p CR(P=0.015)and 40% reached MPR(P=0.094);all CG mice had tumor recurrence(P<0.001),and 50% of them had left lung metastasis(P=0.039).ConclusionsPreoperative and postoperative use of ICI represented by PD-1 monoclonal antibody for neoadjuvant immunotherapy can significantly inhibit the growth of subcutaneous transplanted tumor in mice,reduce the activity of tumor cell proliferation,changed the tumor microenvironment,greatly increase the proportion of mice that achieved PCR and MPR,and reduce postoperative recurrence and metastasis.