O'Konek Jessica J, Ambrosino Elena, Bloom Anja C, Pasquet Lise, Massilamany Chandirasegaran, Xia Zheng, Terabe Masaki, Berzofsky Jay A
Vaccine Branch, CCR, NCI, NIH Bethesda, MD USA.
Mary H. Weiser Food Allergy Center, University of Michigan, Ann Arbor, Michigan, USA.
Oncoimmunology. 2018 Apr 9;7(7):e1439305. doi: 10.1080/2162402X.2018.1439305. eCollection 2018.
A major advantage of immunotherapy of cancer is that effector cells induced at one site should be able to kill metastatic cancer cells in other sites or tissues. However, different tissues have unique immune components, and very little is known about whether effector T cells induced against tumors in one tissue can work against the same tumors in other tissues. Here, we used CT26 murine tumor models to investigate anti-tumor immune responses in the skin and lungs and characterized cross-protection between the two tissues. Blockade of the function of Treg cells with anti-CD25 allowed for T cell-dependent rejection of s.c. tumors. When these mice were simultaneously inoculated i.v. with CT26, they also rejected tumors in the lung. Interestingly, in the absence of s.c. tumors, anti-CD25 treatment alone had no effect on lung tumor growth. These observations suggested that T cell-mediated anti-tumor protective immunity induced against s.c. tumors can also protect against lung metastases of the same tumors. In contrast, NKT cell-deficiency in CD1d mice conferred significant protection against lung tumors but had no effect on the growth of tumors in the skin, and tumor rejection induced against the CT26 in the lung did not confer protection for the same tumor cells in the skin. Thus, effector cells against the same tumor do not work in all tissues, and the induction site of the effector T cells is critical to control metastasis. Further, the regulation of tumor immunity may be different for the same tumor in different anatomical locations.
癌症免疫疗法的一个主要优势在于，在一个部位诱导产生的效应细胞应该能够杀死其他部位或组织中的转移性癌细胞。然而，不同组织具有独特的免疫成分，对于在一个组织中诱导产生的针对肿瘤的效应T细胞是否能对其他组织中的相同肿瘤起作用，人们了解甚少。在此，我们使用CT26小鼠肿瘤模型来研究皮肤和肺部的抗肿瘤免疫反应，并对这两个组织之间的交叉保护作用进行了表征。用抗CD25阻断调节性T细胞（Treg细胞）的功能可实现T细胞依赖性排斥皮下肿瘤。当这些小鼠同时经静脉注射接种CT26时，它们也能排斥肺部肿瘤。有趣的是，在没有皮下肿瘤的情况下，单独进行抗CD25治疗对肺部肿瘤生长没有影响。这些观察结果表明，针对皮下肿瘤诱导产生的T细胞介导的抗肿瘤保护性免疫也可以预防相同肿瘤的肺转移。相比之下，CD1d小鼠中的自然杀伤T细胞（NKT细胞）缺陷对肺部肿瘤具有显著的保护作用，但对皮肤肿瘤的生长没有影响，并且针对肺部CT26诱导产生的肿瘤排斥反应并不能为皮肤中的相同肿瘤细胞提供保护。因此，针对相同肿瘤的效应细胞并非在所有组织中都起作用，效应T细胞的诱导部位对于控制转移至关重要。此外，对于位于不同解剖位置的相同肿瘤，肿瘤免疫的调节可能有所不同。
