Key factors limiting the efficacy of immune-checkpoint blockade and research progress on combined anti-tumor strategies / 中国肿瘤生物治疗杂志

ABSTRACT

@# Immune-checkpoint blockade (ICB) therapy, especially PD-1/PD-L1 and CTLA-4 blocking antibodies, has achieved surprising curative effects in advanced cancer patients. The US FDAhas approved ICB treatment for melanoma, small cell lung carcinoma, kidney carcinoma, and all solid tumors with microsatellite instability. However, with the expansion and deepening of pre-clinical trials and clinical applications in recent years, the limitations of ICB immunotherapy have gradually emerged. For example, even in well-responded tumor types, the effective rate of ICB therapy is only 20%-30%, and there are even cases with tumor progression and metastasis. Therefore, what factors determine or limit the effectiveness of ICB therapy? What kind of patients can benefit from it? Which biomarkers can be used for screening beneficiary patients, evaluating therapeutic outcomes and prognosis? The clarification of above issues will greatly promote the research in this field. In this review, based on the anti-tumor mechanism of ICB, we discuss the recent progress in this field, with an emphasis on the key factors restricting the efficacy of ICB treatment and the current combined therapeutic strategies with ICB, aiming to reveal which biomarkers can be used in the concomitant diagnosis of ICB therapy and the future application perspective of ICB combined therapies, to provide reference for the precision medicine of ICB anti-tumor therapy.