National Center for Cancer Immune Therapy, Department of Oncology, Herlev University Hospital, Herlev, Denmark.
Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
Front Immunol. 2023 Aug 17;14:1240678. doi: 10.3389/fimmu.2023.1240678. eCollection 2023.
Therapeutic cancer vaccination against mutant calreticulin () in patients with -mutant (mut) myeloproliferative neoplasms (MPN) induces strong T-cell responses against mutant CALR yet fails to demonstrate clinical activity. Infiltration of tumor specific T cells into the tumor microenvironment is needed to attain a clinical response to therapeutic cancer vaccination.
Determine if CALRmut specific T cells isolated from vaccinated patients enrich in the bone marrow upon completion of vaccination and explore possible explanations for the lack of enrichment.
CALRmut specific T cells from four of ten vaccinated patients were expanded, enriched, and analyzed by T-cell receptor sequencing (TCRSeq). The TCRs identified were used as fingerprints of CALRmut specific T cells. Bone marrow aspirations from the four patients were acquired at baseline and at the end of trial. T cells were enriched from the bone marrow aspirations and analyzed by TCRSeq to identify the presence and fraction of CALRmut specific T cells at the two different time points. calculations were performed to calculate the ratio between transformed cells and effector cells in patients with mut MPN.
The fraction of CALRmut specific T cells in the bone marrow did not increase upon completion of the vaccination trial. In general, the T cell repertoire in the bone marrow remains relatively constant through the vaccination trial. The enriched and expanded CALRmut specific T cells recognize peripheral blood autologous mut cells. analyses demonstrate a high imbalance in the fraction of mut cells and CALRmut specific effector T-cells in peripheral blood.
CALRmut specific T cells do not enrich in the bone marrow after therapeutic cancer peptide vaccination against mutant CALR. The specific T cells recognize autologous peripheral blood derived mut cells. analyses demonstrate a high imbalance between the number of transformed cells and CALRmut specific effector T-cells in the periphery. We suggest that the high burden of transformed cells in the periphery compared to the number of effector cells could impact the ability of specific T cells to enrich in the bone marrow.
针对 - 突变（mut）骨髓增生性肿瘤（MPN）患者中突变钙网织蛋白（）的治疗性癌症疫苗接种可诱导针对突变 CALR 的强烈 T 细胞反应，但未能显示临床活性。肿瘤特异性 T 细胞浸润肿瘤微环境是实现治疗性癌症疫苗接种临床反应所必需的。
确定从接种疫苗的患者中分离出的 CALRmut 特异性 T 细胞在接种疫苗完成后是否在骨髓中富集，并探讨缺乏富集的可能原因。
从十名接种疫苗的患者中的四名患者中扩增、富集并通过 T 细胞受体测序（TCRSeq）分析 CALRmut 特异性 T 细胞。鉴定的 TCR 被用作 CALRmut 特异性 T 细胞的指纹。在基线和试验结束时从四名患者采集骨髓抽吸物。从骨髓抽吸物中富集 T 细胞，并通过 TCRSeq 分析以确定在两个不同时间点 CALRmut 特异性 T 细胞的存在和分数。计算了 mut MPN 患者中转化细胞与效应细胞之间的比值。
在接种疫苗试验完成时，骨髓中 CALRmut 特异性 T 细胞的分数没有增加。一般来说，在整个疫苗接种试验过程中，骨髓中的 T 细胞库保持相对稳定。经富集和扩增的 CALRmut 特异性 T 细胞可识别外周血自体 mut 细胞。分析表明，外周血中 mut 细胞和 CALRmut 特异性效应 T 细胞的分数存在高度不平衡。
针对突变 CALR 的治疗性癌症肽疫苗接种后，CALRmut 特异性 T 细胞不会在骨髓中富集。特异性 T 细胞识别自体外周血衍生的 mut 细胞。分析表明，外周血中转化细胞和 CALRmut 特异性效应 T 细胞的数量之间存在高度不平衡。我们认为，与效应细胞数量相比，外周血中转化细胞的高负担可能会影响特异性 T 细胞在骨髓中富集的能力。
Zotero 插件
