LAUSR

Simple Summary Signal transducer and activator of transcription 3 (STAT3) plays a critical role in the development and progression of non-small cell lung cancer (NSCLC) tumors. Several reports suggest that STAT3 is involved in immunosuppression and the promotion of resistance to immune checkpoint inhibitors. In this review, we discuss the potential therapeutic strategy of combining STAT3 inhibition with immune checkpoint inhibitors to overcome drug resistance and enhance their efficacy in NSCLC. Abstract Despite recent therapeutic advances, non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related death. Signal transducer and activator of transcription 3 (STAT3) is a transcription factor (TF) with multiple tumor-promoting effects in NSCLC, including proliferation, anti-apoptosis, angiogenesis, invasion, metastasis, immunosuppression, and drug resistance. Recent studies suggest that STAT3 activation contributes to resistance to immune checkpoint inhibitors. Thus, STAT3 represents an attractive target whose pharmacological modulation in NSCLC may assist in enhancing the efficacy of or overcoming resistance to immune checkpoint inhibitors. In this review, we discuss the biological mechanisms through which STAT3 inhibition synergizes with or overcomes resistance to immune checkpoint inhibitors and highlight the therapeutic strategy of using drugs that target STAT3 as potential combination partners for immune checkpoint inhibitors in the management of NSCLC patients.