Adoptive cell transfer (ACT) is a type of immunotherapy that uses a patient's own T lymphocytes to recognize and attack cancer. ACT has been effective in treating certain patients with metastatic melanoma and is being applied to treat some epithelial cancers. Krishna et al. investigated why some cancer patients respond to ACT, whereas others do not. They identified a population of CD8+ T cells that had stem-like surface markers that were associated with effective tumor cell killing and favorable response of melanoma patients to ACT. Only a small subset of T cells specific against tumor mutations were found in this stem-like state, whereas most mutation-reactive T cells were terminally differentiated. These findings could be of value in improving cancer immunotherapy outcomes.
Adoptive T cell therapy (ACT) using ex vivo–expanded autologous tumor-infiltrating lymphocytes (TILs) can mediate complete regression of certain human cancers. The impact of TIL phenotypes on clinical success of TIL-ACT is currently unclear. Using high-dimensional analysis of human ACT products, we identified a memory-progenitor CD39-negative stem-like phenotype (CD39−CD69−) associated with complete cancer regression and TIL persistence and a terminally differentiated CD39-positive state (CD39+CD69+) associated with poor TIL persistence. Most antitumor neoantigen-reactive TILs were found in the differentiated CD39+ state. However, ACT responders retained a pool of CD39− stem-like neoantigen-specific TILs that was lacking in ACT nonresponders. Tumor-reactive stem-like TILs were capable of self-renewal, expansion, persistence, and superior antitumor response in vivo. These data suggest that TIL subsets mediating ACT response are distinct from TIL subsets enriched for antitumor reactivity.
过继细胞转移（ACT）是一种免疫疗法，利用患者自身的T淋巴细胞识别并攻击癌症。ACT在治疗某些转移性黑色素瘤患者方面已显示出疗效，并正被应用于治疗一些上皮癌。Krishna等人研究了为何一些癌症患者对ACT有反应，而另一些则没有。他们发现了一群具有干细胞样表面标志物的CD8+ T细胞，这些标志物与有效的肿瘤细胞杀伤以及黑色素瘤患者对ACT的良好反应相关。只有一小部分针对肿瘤突变特异的T细胞处于这种干细胞样状态，而大多数突变反应性T细胞已终末分化。这些发现对于改善癌症免疫治疗结果可能具有价值。
使用离体扩增的自体肿瘤浸润淋巴细胞（TILs）的过继T细胞疗法（ACT）可介导某些人类癌症的完全消退。目前，TIL表型对TIL-ACT临床成功的影响尚不清楚。通过对人类ACT产品进行高维分析，我们鉴定出一种与癌症完全消退和TIL持久性相关的记忆祖细胞CD39阴性干细胞样表型（CD39−CD69−），以及一种与TIL持久性差相关的终末分化CD39阳性状态（CD39+CD69+）。大多数抗肿瘤新抗原反应性TILs处于分化状态的CD39+状态。然而，ACT有反应者保留了一个CD39−干细胞样新抗原特异性TILs库，而ACT无反应者则缺乏该库。肿瘤反应性干细胞样TILs能够在体内自我更新、扩增、持久存在并具有优异的抗肿瘤反应。这些数据表明，介导ACT反应的TIL亚群与富集抗肿瘤反应性的TIL亚群是不同的。
Stem-like CD8 T cells mediate response of adoptive cell immunotherapy against human cancer
肿瘤(癌症)患者之家