Xu Jiazhi, Apetoh Lionel
Microbiology and Immunology, Indiana University Indianapolis, Indianapolis, Indiana, USA.
Microbiology and Immunology, Indiana University Indianapolis, Indianapolis, Indiana, USA
J Immunother Cancer. 2025 Apr 28;13(4):e011522. doi: 10.1136/jitc-2025-011522.
Antibodies against immune checkpoints are now routinely administered as a first line of treatment against metastatic lung cancer. Resistance to immune checkpoint inhibitors is, however, frequent, underscoring the need to find alternative treatments. Adoptive T-cell therapy has recently proven effective in treating patient's refractory to immune checkpoint inhibitors. This provides impetus to characterize the T-cell subsets best able to tackle tumors. The anticancer activities of IL-9-producing CD4 T helper cells (T9 cells) were identified in melanoma in 2012. T9 cells feature strong antimelanoma effects thanks to their production of interleukin (IL)-9 and the activation of innate and adaptive immune effectors. The ability of T9 cells to prevent the growth of triple-negative breast cancer (TNBC) and osteosarcoma (OS), which commonly metastasize to the lungs, is elusive. In this commentary, we discuss the findings of Chen reported in the JITC demonstrating that T9 cells are lung-tropic and eliminate TNBC and OS cells developing in the lungs. We also highlight how these investigations are in line with recent studies indicating that the adoptive transfer of IL-9-producing T cells eliminate aggressive cancers, including hematological tumors like leukemia and solid tumors such as glioblastoma. Altogether, these findings over the past 13 years support the clinical evaluation of T9 cells in the adoptive therapy of cancer.
针对免疫检查点的抗体目前已常规用作转移性肺癌的一线治疗药物。然而,对免疫检查点抑制剂产生耐药性的情况很常见,这凸显了寻找替代治疗方法的必要性。过继性T细胞疗法最近已被证明在治疗对免疫检查点抑制剂难治的患者方面有效。这为确定最能对抗肿瘤的T细胞亚群提供了动力。2012年在黑色素瘤中发现了产生白细胞介素-9(IL-9)的CD4辅助性T细胞(T9细胞)的抗癌活性。T9细胞由于产生IL-9以及激活先天性和适应性免疫效应细胞而具有强大的抗黑色素瘤作用。T9细胞预防通常转移至肺部的三阴性乳腺癌(TNBC)和骨肉瘤(OS)生长的能力尚不清楚。在这篇评论中,我们讨论了Chen在《Journal for ImmunoTherapy of Cancer》上发表的研究结果,该结果表明T9细胞具有肺嗜性,并能消除在肺部生长的TNBC和OS细胞。我们还强调了这些研究如何与最近的研究一致,这些研究表明过继转移产生IL-9的T细胞可消除侵袭性癌症,包括白血病等血液肿瘤和胶质母细胞瘤等实体瘤。总之,过去13年的这些研究结果支持对T9细胞在癌症过继治疗中的临床评估。