非小细胞肺癌放疗联合免疫治疗的研究进展与挑战

由于部分晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者在免疫治疗后没有产生免疫应答或发生继发性耐药,NSCLC免疫治疗的疗效仍不能令人满意。因此,研究者们开展了多项包括放疗(radiation therapy,RT)联合免疫治疗在内的、致力于增强免疫治疗疗效方法的研究。本研究回顾分析了放疗联合免疫治疗提高NSCLC疗效相关研究的进展,并探索进一步增强这一联合治疗疗效的新途径。首先,我们讨论了目前仅有的两项随机试验(和一项汇总分析)。这些试验表明,免疫治疗联合放疗可提高转移性NSCLC患者的远隔客观缓解率、无进展生存期和总生存期。然后,讨论了与放疗免疫疗效相关的因素和生物标志物,例如低水平的程序性细胞死亡配体1(programmed cell death ligand 1,PD-L1)、肿瘤突变负荷(tumor mutational burden,TMB)和患者免疫功能。接下来,我们讨论了放疗逆转免疫治疗耐药的机制和应对措施。最后,讨论了低剂量放疗有助于调控肿瘤间质中抑制T细胞浸润的抑制信号的新作用。综上所述,通过对上述研究的深入分析使更多NSCLC患者从免疫治疗中获益。

On the immunological limitations of hibernation and synthetic torpor as a supporting technique for astronauts’ radioprotection in deep space missions

Although human hibernation has been introduced as an effective technique in space exploration,there are concerns regarding the intrinsic risks of the approach(i.e.,synthetic torpor)and other factors involved in this procedure.Besides concerns about the brain changes and the state of consciousness during hibernation,an"Achilles heel"of the hibernation is the negative impact of torpor on factors such as the number of circulating leukocytes,complement levels,response to lipopolysaccharides,phagocytotic capacity,cytokine production,lymphocyte proliferation,and antibody production.Moreover,increased virulence of bacteria in deep space can significantly increase the risk of infection.The increased infection risk during long-term space missions with the combined effects of radiation and microgravity affect the astronauts’immune system.With these additional immune system stressors,torpor-induced extraimmunosuppression can be potentially life threatening for astronauts.

Combined treatment of non-small cell lung cancer using radiotherapy and immunotherapy: challenges and updates

The efficacy of immunotherapy for advanced non-small cell lung cancer(NSCLC)remains unsatisfactory,as the majority of patients either do not experience an objective response or acquire secondary resistance.As a result,several methods to enhance the systemic efficacy of immunotherapy have been investigated,including a large area of active research by combining immunotherapy with radiation therapy(RT).Given the rapidly burgeoning concept of combining immunotherapy and RT for increasing therapeutic benefit,we review the progress in this field thus far and explore further avenues for enhancing this combination.This review commences with a discussion of the only two existing randomized trials(and a pooled analysis)showing that the addition of RT to immunotherapy improves the abscopal response rate,progression-free survival,and overall survival in metastatic NSCLC patients.We then discussed factors and biomarkers that may be associated with a proportionally greater benefit to additional RT,such as low programmed cell death protein ligand 1(PD-L1)status,tumor mutational burden(TMB),and patient’s immune function.Next,the implementation of RT to overcome immunotherapy resistance is discussed,including a mechanistic discussion and methods with which these mechanisms could be exploited.Lastly,the emerging role of low-dose RT is discussed,which may help to overcome inhibitory signals in the tumor stroma that limit T-cell infiltration.Taken together,given the current state of this rapidly expanding realm,these futuristic strategies may be reflected upon to further enhance the efficacy of immunotherapy for a wider group of patients.