非小细胞肺癌免疫耐药机制及应对策略的研究进展

免疫治疗对非小细胞肺癌(non-small cell lung cancer,NSCLC)有显著的临床益处,然而,随着NSCLC免疫治疗的广泛应用,免疫耐药成为不可避免的问题。免疫治疗诱导肿瘤微环境发生广泛的细胞和分子改变,其耐药机制目前尚未完全明确,且耐药后标准化疗方案的疗效有限,亟待探索基于耐药机制的更有效的应对策略。本文拟对目前已知的免疫治疗耐药机制及应对策略进行综述,为临床医生制定更加个体化、精准化的治疗方案以及改善患者预后提供基础。

Safety, immunogenicity and protective effectiveness of heterologous boost with a recombinant COVID-19 vaccine (Sf9 cells) in adult recipients of inactivated vaccines

Vaccines have proven effective in protecting populations against COVID-19,including the recombinant COVID-19 vaccine(Sf9 cells),the first approved recombinant protein vaccine in China.In this positive-controlled trial with 85 adult participants(Sf9 cells group:n=44;CoronaVac group:n=41),we evaluated the safety,immunogenicity,and protective effectiveness of a heterologous boost with the Sf9 cells vaccine in adults who had been vaccinated with the inactivated vaccine,and found a post-booster adverse events rate of 20.45%in the Sf9 cells group and 31.71%in the CoronaVac group(p=0.279),within 28 days after booster injection.Neither group reported any severe adverse events.Following the Sf9 cells vaccine booster,the geometric mean titer(GMT)of binding antibodies to the receptor-binding domain of prototype SARS-CoV-2 on day 28 post-booster was significantly higher than that induced by the CoronaVac vaccine booster(100,683.37 vs.9,451.69,p<0.001).In the Sf9 cells group,GMTs of neutralizing antibodies against pseudo SARS-CoV-2 viruses(prototype and diverse variants of concern[VOCs])increased by 22.23–75.93 folds from baseline to day 28 post-booster,while the CoronaVac group showed increases of only 3.29–10.70 folds.Similarly,neutralizing antibodies against live SARS-CoV-2 viruses(prototype and diverse VOCs)increased by 68.18–192.67 folds on day 14 post-booster compared with the baseline level,significantly greater than the CoronaVac group(19.67–37.67 folds).A more robust Th1 cellular response was observed with the Sf9 cells booster on day 14 post-booster(mean IFN-γ+spot-forming cells per 2×105 peripheral blood mononuclear cells:26.66 vs.13.59).Protective effectiveness against symptomatic COVID-19 was approximately twice as high in the Sf9 cells group compared to the CoronaVac group(68.18%vs.36.59%,p=0.004).Our study findings support the high protective effectiveness of heterologous boosting with the recombinant COVID-19 vaccine(Sf9 cells)against symptomatic COVID-19 of diverse SARS-CoV-2 variants of concern,while causing no apparent safety concerns.

Comparing T-and B-cell responses to COVID-19 vaccines across varied immune backgrounds

The emergence of adapted variants of the SARS-CoV-2 virus has led to a surge in breakthrough infections worldwide.A recent analysis of immune responses in people who received inactivated vaccines has revealed that individuals with no prior infection have limited resistance to Omicron and its sub-lineages,while those with previous infections exhibit a significant amount of neutralizing antibodies and memory B cells.However,specific T-cell responses remain largely unaffected by the mutations,indicating that T-cell-mediated cellular immunity can still provide protection.Moreover,the administration of a third dose of vaccine has resulted in a marked increase in the spectrum and duration of neutralizing antibodies and memory B cells in vivo,which has enhanced resistance to emerging variants such as BA.2.75 and BA.2.12.1.These results highlight the need to consider booster immunization for previously infected individuals and the development of novel vaccination strategies.The rapid spread of adapted variants of the SARS-CoV-2 virus presents a significant challenge to global health.The findings from this study underscore the importance of tailoring vaccination strategies based on individual immune backgrounds and the potential need for booster shots to combat emerging variants.Continued research and development are crucial to discovering new immunization strategies that will effectively protect public health against the evolving virus.