The link between carcinogen exposure and cancer immunogenicity is unclear. Single exposure to 12-dimethylbenz[a]anthracene (DMBA) at puberty accelerated spontaneous breast carcinogenesis in mouse mammary tumor virus-polyoma middle tumor-antigen transgenic (MMTV-PyMT^tg or PyMT) and MMTV-Her2/neu^tg (Her2) mice. Paradoxically, DMBA-treated PyMT and Her2 animals were protected from metastasis. CD8⁺ T cells significantly infiltrated DMBA-exposed breast cancers. CD8⁺ T cell depletion resulted in severe lung and liver metastasis in DMBA-treated PyMT mice. Besides increasing tumor mutational burden, DMBA exposure up-regulated Chemokine (C-C motif) ligand 21 (CCL21) in cancer cells and heightened antigen presentation. CCL21 injection suppressed breast cancer growth, and CCL21 receptor deletion attenuated T cell immunity against cancer metastasis in DMBA-treated PyMT animals. CCL21 expression correlated with increased mutational burden and cytolytic activity across human cancers. Higher CCL21 levels correlated with increased CD8⁺ T cell infiltrates in human breast cancer and predicted lower breast cancer distant recurrence rate. Collectively, carcinogen exposure induces immune-activating factors within cancer cells that promote CD8⁺ T cell immunity against metastasis.

致癌物暴露与癌症免疫原性之间的联系尚不清楚。青春期单次暴露于 12-二甲基苯并[a]蒽 (DMBA) 可加速小鼠乳腺肿瘤病毒-多瘤中间肿瘤抗原转基因 (MMTV-PyMT ^tg或 PyMT) 和 MMTV-Her2/neu ^tg (Her2) 小鼠的自发性乳腺癌发生。矛盾的是，DMBA 治疗的 PyMT 和 Her2 动物却免受转移。 CD8 ⁺ T 细胞显着浸润 DMBA 暴露的乳腺癌。 CD8 ⁺ T 细胞耗竭导致 DMBA 治疗的 PyMT 小鼠出现严重的肺和肝转移。除了增加肿瘤突变负担外，DMBA 暴露还会上调癌细胞中的趋化因子（CC 基序）配体 21 (CCL21) 并增强抗原呈递。在 DMBA 处理的 PyMT 动物中，CCL21 注射可抑制乳腺癌生长，CCL21 受体缺失会减弱针对癌症转移的 T 细胞免疫。 CCL21表达与人类癌症中突变负荷和细胞溶解活性的增加相关。较高的 CCL21 水平与人类乳腺癌中 CD8 ⁺ T 细胞浸润增加相关，并预测较低的乳腺癌远处复发率。总的来说，致癌物暴露会诱导癌细胞内产生免疫激活因子，从而促进 CD8 ⁺ T 细胞免疫抵抗转移。