Objective To explore the possible mechanism of Yiqi Yangyin Jiedu Formula（益气养阴解毒方

YYJF） in treatment of lung cancer. Methods LLC-luc cells in logarithmic period were injected into the left lung of C57 BL/6 mice to establish the model of orthotopic lung cancer. Forty-eight successfully modeled mice were randomized into model group

low

medium and high dose YYJF groups

monoclonal antibody group

and combination group with eight mice in each group. The mice in model group received 0.4 ml normal saline by gavage; the low

medium and high dose YYJF groups were given 47

94 and 188 g/（kg·d） YYJF by gavage respectively and intraperitoneal injection of 0.3 ml normal saline; the monoclonal antibody group received intraperitoneal injection of 0.3 ml anti-cytotoxic T lymphocyte-associated antigen 4（CTLA-4） monoclonal antibody and 0.4 ml normal saline by gavage

totally for three times; the combined group was administered with medium YYJF by gavage and intraperitoneal injection of anti CTLA-4 monoclonal antibody

with same dosage mentioned above; the intervention in all the groups lasted for 21 days. In vivo optical imaging system was used to monitor the tumor growth of mice and detect the fluorescence intensity in tumor tissue; survival time was assessed. HE staining method was applied to observe the morphology of tumor cells; immunohistochemical method was used to detect the protein expression of forkhead winged helix transcription factor P3（Foxp3） and CTLA-4. Results Compared to model group

the medium and high dose YYJF group

the monoclonal antibody group and the combined group had decreased mean fluorescence intensity（MFI） in tumor tissue（P<0.05）

of which the combined group had lowest MFI（P<0.05）. HE staining results showed that poorly differentiated adenocarcinoma cells were intensely distributed in the tumor tissues of model group and low dose YYJF group

and increased pathological mitotic figures were seen; the pathological mitotic figures decreased in medium and high dose YYJF groups and monoclonal antibody group

and decreased to the lowest in the combined group. The median survival time of model group

low

medium and high dose YYJF groups

monoclonal antibody group and the combined group was 21

24

31

32

96

130 days

respectively. Compared to model group

the medium and high dose YYJF groups

monoclonal antibody group and the combined group had longer survival time and lower Foxp3 and CTLA-4 protein expression in tumor tissues（P<0.05）; the survival time was significantly longer in the combined group than in the medium YYJF group（P<0.01）; the expression of Foxp3 and CTLA-4 protein was significantly lower in combined group than in high dose YYJF group（P<0.05）. Conclusion YYJF combined with anti CTLA-4 monoclonal antibody in synergistic interaction can inhibit the tumor growth and prolong survival time in treating mice model of orthotopic lung cancer. The mechanism may be related to the reversion of immunosuppression of cancer microenviroment.