The impact of tumor immunogenicity on cancer pain phenotype using syngeneic oral cancer mouse models.
The impact of tumor immunogenicity on cancer pain phenotype using syngeneic oral cancer mouse models.
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DOI：
10.3389/fpain.2022.991725
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发表时间：
2022
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头颈部鳞状细胞癌(HNSCC)患者报告原发肿瘤部位严重的功能性疼痛。目前的假说是，口腔癌疼痛是由于肿瘤细胞和周围免疫细胞分泌的致敏介质使支配肿瘤的初级感觉神经元敏化而在癌症微环境中启动和维持的。免疫原性，即诱导适应性免疫反应的能力，已经通过癌细胞移植实验得到了广泛的研究。然而，口腔癌疼痛的研究主要使用异种移植模型，在这种模型中，人类来源的肿瘤细胞接种到缺乏适应性免疫反应的裸鼠体内；炎症在口腔癌症诱导的伤害性反应中的作用仍不清楚。利用同基因口腔癌小鼠模型，研究肿瘤细胞的免疫原性和生长对口腔面部伤害性行为和口腔癌诱导的感觉神经元可塑性的影响。我们发现，侵袭性、弱免疫原性的小鼠口腔癌细胞系MOC2在雄性和雌性C57BL/6小鼠中都能诱导快速的口面部伤害性行为。此外，MOC2肿瘤的生长在三叉神经节中引发了实质性的损伤反应，其定义是舌神经三叉神经细胞中损伤反应标记ATF3的显著上调。相比之下，使用高免疫原性的小鼠口腔癌细胞株MOC1，我们发现只有雌性C57BL/6小鼠的口面部伤害性行为发生得慢得多，而且舌神经支配感觉神经元中肿瘤相关免疫环境和基因调控的性别差异。总之，这些数据表明，癌症诱导的伤害性行为和感觉神经元的可塑性在很大程度上取决于癌细胞系的免疫原性表型和相关的免疫反应。
Head and neck squamous cell carcinoma (HNSCC) patients report severe function-induced pain at the site of the primary tumor. The current hypothesis is that oral cancer pain is initiated and maintained in the cancer microenvironment due to secretion of algogenic mediators from tumor cells and surrounding immune cells that sensitize the primary sensory neurons innervating the tumor. Immunogenicity, which is the ability to induce an adaptive immune response, has been widely studied using cancer cell transplantation experiments. However, oral cancer pain studies have primarily used xenograft transplant models in which human-derived tumor cells are inoculated in an athymic mouse lacking an adaptive immune response; the role of inflammation in oral cancer-induced nociception is still unknown. Using syngeneic oral cancer mouse models, we investigated the impact of tumor cell immunogenicity and growth on orofacial nociceptive behavior and oral cancer-induced sensory neuron plasticity. We found that an aggressive, weakly immunogenic mouse oral cancer cell line, MOC2, induced rapid orofacial nociceptive behavior in both male and female C57Bl/6 mice. Additionally, MOC2 tumor growth invoked a substantial injury response in the trigeminal ganglia as defined by a significant upregulation of injury response marker ATF3 in tongue-innervating trigeminal neurons. In contrast, using a highly immunogenic mouse oral cancer cell line, MOC1, we found a much slower onset of orofacial nociceptive behavior in female C57Bl/6 mice only as well as sex-specific differences in the tumor-associated immune landscape and gene regulation in tongue innervating sensory neurons. Together, these data suggest that cancer-induced nociceptive behavior and sensory neuron plasticity can greatly depend on the immunogenic phenotype of the cancer cell line and the associated immune response.
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影响因子：
5.1
作者：
Ahlström FHG;Mätlik K;Viisanen H;Blomqvist KJ;Liu X;Lilius TO;Sidorova Y;Kalso EA;Rauhala PV
通讯作者：
Rauhala PV
影响因子：
4
作者：
Connelly, ST;Schmidt, BL
通讯作者：
Schmidt, BL
影响因子：
3.4
作者：
Judd, Nancy P.;Allen, Clint T.;Uppaluri, Ravindra
通讯作者：
Uppaluri, Ravindra
影响因子：
14.9
作者：
Elmusrati A;Wang J;Wang CY
通讯作者：
Wang CY
影响因子：
3.7
作者：
Doré-Savard L;Otis V;Belleville K;Lemire M;Archambault M;Tremblay L;Beaudoin JF;Beaudet N;Lecomte R;Lepage M;Gendron L;Sarret P
通讯作者：
Sarret P