Circulation and homing of melanoma-reactive T cells to both cutaneous and visceral metastases after vaccination with monocyte-derived dendritic cells
Circulation and homing of melanoma-reactive T cells to both cutaneous and visceral metastases after vaccination with monocyte-derived dendritic cells
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DOI：
10.1002/ijc.20238
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发表时间：
2004-08-20
影响因子：
6.4
通讯作者：
Becker, JC
中科院分区：
文献类型：
--
作者：
Berger, TG;Haendle, I;Becker, JC
抗癌免疫疗法旨在诱导肿瘤特异性T细胞，最终杀死肿瘤细胞。因此，效应细胞不仅应发挥细胞毒活性，还应归巢并渗透到肿瘤部位。因此，免疫调节治疗的监测不应限于外周血单核细胞（PBMC）的循环池，还应包括肿瘤浸润淋巴细胞（TIL），以及这些发现与临床过程的相关性。我们在这里报告的纵向免疫检查的黑色素瘤患者谁开发了显着有效的体外可检测的抗黑色素瘤细胞毒性T细胞（CTL）反应后，自体肽脉冲树突状细胞接种。据我们所知，这种对多种肿瘤抗原的有效CTL应答以前在黑色素瘤患者中没有描述过，无论是自发的还是在任何治疗后。该患者首先经历了对治疗的短暂反应，但最终死于疾病进展并死亡。进展与循环中和皮肤转移处的肿瘤反应性T细胞数量的下降以及MHC I类抗原的丢失有关。免疫学分析显示，在相对稳定的疾病阶段，该患者的外周血中存在全功能的肿瘤特异性T细胞，原位四聚体染色表明，这些细胞也聚集在皮肤和内脏肿瘤部位。此外，PBMC和TIL的比较克隆型作图描绘了这2个隔室之间重叠的TCR库使用。由于在该患者中观察到的强CTL应答是癌症疫苗接种的目标，但到目前为止仅很少观察到，因此对表现出异常临床和/或免疫学应答的患者进行彻底分析对于理解疫苗疗法如何起作用以及如何进一步改进似乎至关重要。(C)2004 Wiley-Liss，Inc.
Anticancer immune therapies aim at the induction of tumor-specific T cells, which ultimately should kill tumor cells. The effector cells should, therefore, not only exert cytotoxic activity but also home to and infiltrate the tumor site. Hence, monitoring of immune modulating therapies should not be restricted to the circulating pool of peripheral blood mononuclear cells (PBMC) but also include tumor-infiltrating lymphocytes (TIL), as well as the correlation of these findings to the clinical course. We report here on the longitudinal immunologic workup of a melanoma patient who developed remarkably potent ex vivo detectable antimelanoma cytotoxic T-cell (CTL) responses after vaccinations with autologous peptide-pulsed dendritic cells. Such potent CTL responses to multiple tumor antigens have, to the best of our knowledge, not been described previously in melanoma patients, neither spontaneously nor after any therapy. This patient first experienced a transient response to therapy but finally succumbed to disease progression and died. Progression was associated with the decline of the numbers of tumor-reactive T cells in circulation and at skin metastases in addition to the loss of MHC class I antigens. The immunologic analysis revealed that fully functional tumor-specific T cells were present in the peripheral blood of this patient during the phase of a relatively stable disease, and in situ tetramer staining demonstrated that these cells were also accumulated at cutaneous and visceral tumor sites. Furthermore, comparative clonotype mapping of PBMC and TIL depicted an overlapping TCR repertoire usage among these 2 compartments. Since strong CTL responses as observed in this patient are the goal of cancer vaccination but are so far only rarely observed, the thorough analysis of patients exhibiting either exceptional clinical and/or immunologic responses appears critical to understanding how vaccine therapies work and can be further improved. (C) 2004 Wiley-Liss, Inc.