Abstract
The development of therapeutic strategies to overcome resistance to anti-PD1 therapies in lung cancer remains a significant challenge. Based on our recent findings of SH003's immunomodulatory capabilities, this study investigates the combined effects of SH003 and docetaxel (DTX) as a potential second-line therapy in an anti-PD1-resistant lung cancer model. Our results demonstrate that SH003 and DTX effectively inhibit tumor growth by inducing apoptosis in an anti-PD1-resistant lung cancer LLC1 model, while enhancing the infiltration of cytotoxic CD8(+) T cells and NK cells into the tumor microenvironment (TME), thereby boosting anti-tumor immunity. SH003 also exhibited immunomodulatory effects in an immunosuppressed mouse model, further emphasizing its potential in enhancing immune responses. Notably, the combination treatment significantly inhibits tumor growth by targeting the EGFR/JAK/STAT3 signaling pathway, contributing to the reduction of PD-L1 expression associated with immune evasion. These findings elucidate the dual mechanism of action of the SH003-DTX combination in overcoming resistance through both direct anticancer effects and immune system modulation. Overall, these findings demonstrate that the SH003-DTX combination presents a promising approach for anti-PD1-refractory lung cancer patients, potentially offering new treatment possibilities where current options are limited.