Division of Molecular Oncology and Immunology, The Netherlands Cancer Institute, Amsterdam, Netherlands.
Department of Medical Microbiology and Infection Prevention, University Medical Centre Groningen, Groningen, Netherlands.
Front Immunol. 2024 Aug 27;15:1447555. doi: 10.3389/fimmu.2024.1447555. eCollection 2024.
Research has confirmed the safety and comparable seroconversion rates following SARS-CoV-2 vaccination in patients with solid cancers. However, the impact of cancer treatment on vaccine-induced T cell responses remains poorly understood.
In this study, we expand on previous findings within the VOICE trial by evaluating the functional and phenotypic composition of mRNA-1273-induced T cell responses in patients with solid tumors undergoing immunotherapy, chemotherapy, or both, compared to individuals without cancer. We conducted an ELISpot analysis on 386 participants to assess spike-specific T cell responses 28 days after full vaccination. Further in-depth characterization of using flow cytometry was performed on a subset of 63 participants to analyze the functional phenotype and differentiation state of spike-specific T cell responses.
ELISpot analysis showed robust induction of spike-specific T cell responses across all treatment groups, with response rates ranging from 75% to 80%. Flow cytometry analysis revealed a distinctive cytokine production pattern across cohorts, with CD4 T cells producing IFNγ, TNF, and IL-2, and CD8 T cells producing IFNγ, TNF, and CCL4. Variations were observed in the proportion of monofunctional CD4 T cells producing TNF, particularly higher in individuals without cancer and patients treated with chemotherapy alone, while those treated with immunotherapy or chemoimmunotherapy predominantly produced IFNγ. Despite these differences, polyfunctional spike-specific memory CD4 and CD8 T cell responses were comparable across cohorts. Notably, immunotherapy-treated patients exhibited an expansion of spike-specific CD4 T cells with a terminally differentiated effector memory phenotype.
These findings demonstrate that systemic treatment in patients with solid tumors does not compromise the quality of polyfunctional mRNA-1273-induced T cell responses. This underscores the importance of COVID-19 vaccination in patients with solid cancers undergoing systemic treatment.
研究已经证实，在实体瘤患者中，接种 SARS-CoV-2 疫苗是安全的，并且能够产生相当的血清转化率。然而，癌症治疗对疫苗诱导的 T 细胞反应的影响仍知之甚少。
在这项研究中，我们扩展了之前在 VOICE 试验中的发现，评估了正在接受免疫治疗、化疗或两者联合治疗的实体瘤患者与无癌症个体相比，mRNA-1273 诱导的 T 细胞反应的功能和表型组成。我们对 386 名参与者进行了 ELISpot 分析，以评估完全接种疫苗后 28 天的刺突特异性 T 细胞反应。我们对 63 名参与者中的一部分进行了更深入的流式细胞术分析，以分析刺突特异性 T 细胞反应的功能表型和分化状态。
ELISpot 分析显示，所有治疗组均能强烈诱导刺突特异性 T 细胞反应，反应率在 75%至 80%之间。流式细胞术分析揭示了各队列之间独特的细胞因子产生模式，CD4 T 细胞产生 IFNγ、TNF 和 IL-2，CD8 T 细胞产生 IFNγ、TNF 和 CCL4。在产生 TNF 的单功能 CD4 T 细胞的比例方面观察到了变化，特别是在无癌症和单独接受化疗的个体中更高，而接受免疫治疗或化疗免疫治疗的个体主要产生 IFNγ。尽管存在这些差异，但多能刺突特异性记忆 CD4 和 CD8 T 细胞反应在各队列中是可比的。值得注意的是，接受免疫治疗的患者表现出特异性 CD4 T 细胞的扩增，具有终末分化的效应记忆表型。
这些发现表明，在实体瘤患者中，全身治疗并不影响多能 mRNA-1273 诱导的 T 细胞反应的质量。这突显了在接受全身治疗的实体癌患者中接种 COVID-19 疫苗的重要性。
