摘要:手术切除转移性病变可增加III期黑色素瘤患者t细胞对肿瘤相关抗原的反应性

Y. Coaña, Fríða Björk Gunnarsdóttir, Maria Wolodarski, S. E. Brage, G. Masucci, J. Hansson, R. Kiessling
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摘要

目前,几乎没有任何外周血生物标志物可以识别晚期黑色素瘤患者的预后或生存。我们的主要目的是比较III期或IV期转移性黑色素瘤患者在转移病灶切除手术前后外周血T细胞对肿瘤相关抗原的反应性。从手术前后采集的血液样本中分离外周血单个核细胞,并在两周内用三种已知黑色素瘤抗原(MelanA, NY-ESO-1和Cripto-1)重叠的肽池刺激。12天后,再次刺激细胞,用多色流式细胞术分析。分析CD4和CD8阳性细胞的细胞因子产生情况。McNemar试验分析手术前后的变化,Kaplan Meier分析细胞反应性和细胞因子产生与无进展生存期的相关性。手术切除转移灶改变了T细胞对MelanA、NY-ESO-1和Cripto-1的反应性。刺激后产生IL-17和/或TNF-a的CD4 T细胞的存在与较差的无进展生存期(PFS)相关。我们在这里表明,手术切除转移瘤增加了黑色素瘤患者的t细胞反应性,某些细胞因子谱可能与PFS有关。这可以深入了解特异性t细胞反应和对转移性黑色素瘤有利的免疫反应之间的复杂关系。引文格式:Yago Pico de Coana, frizha Bjork Gunnarsdottir, Maria Wolodarski, Suzanne Egyhazi Brage, Giuseppe Masucci, Johan Hansson, Rolf Kiessling。在III期黑色素瘤患者中,手术切除转移性病变可增加t细胞对肿瘤相关抗原的反应性[摘要]。摘自:AACR肿瘤免疫学和免疫治疗特别会议论文集;2017年10月1-4日;波士顿,MA。费城(PA): AACR;癌症免疫学杂志,2018;6(9增刊):摘要nr A14。
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Abstract A14: Surgical removal of metastatic lesions increases T-cell reactivity to tumor-associated antigens in stage III melanoma patients
Currently, there are hardly any peripheral blood biomarkers that allow for identification of patients’ prognosis or survival in advanced melanoma patients. Our main objective was to compare the reactivity of peripheral blood T cells of patients with stage III or IV metastatic melanoma to Tumor-Associated Antigens, before and after surgery where metastatic lesions were removed. Peripheral blood mononuclear cells were isolated from blood samples taken before and after surgery and were stimulated over the course of two weeks with overlapping peptide pools of three known melanoma antigens: MelanA, NY-ESO-1, and Cripto-1. After 12 days, cells were re-stimulated and analyzed using multicolor flow cytometry. CD4 and CD8 positive cells were analyzed for cytokine production. McNemar’s test was used to analyze changes before and after surgery, and correlation between cell reactivity and cytokine production with progression free survival was determined by Kaplan Meier analysis. Surgical removal of metastatic lesions changed reactivity of T cells to MelanA, NY-ESO-1 and Cripto-1. The presence of CD4 T cells that produced IL-17 and/or TNF-a after stimulation was correlated with a worse progression-free survival (PFS). We show here that surgical removal of metastases increases T-cell reactivity in melanoma patients and that certain cytokine profiles may be associated to PFS. This could provide insight into the complexity of the correlation between a specific T-cell response and a favorable immune response to metastatic melanoma. Citation Format: Yago Pico de Coana, Friða Bjork Gunnarsdottir, Maria Wolodarski, Suzanne Egyhazi Brage, Giuseppe Masucci, Johan Hansson, Rolf Kiessling. Surgical removal of metastatic lesions increases T-cell reactivity to tumor-associated antigens in stage III melanoma patients [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr A14.
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