Background/Objectives: Non-melanoma skin cancer, which includes cutaneous squamous cell carcinoma (cSCC), ranks as the 5th most common cancer globally with high morbidity and more total deaths than melanoma despite having a lower mortality rate. While most cSCC cases can be treated with surgery, locally advanced, metastatic, and high-risk cSCC tumors are associated with a worse prognosis with higher rates of recurrence and require multimodality therapy. However, there is limited data on animal models of cutaneous squamous cell carcinoma for the use of combinatory immunotherapy and radiation.Methods: In this study, spontaneously generated tumors using DMBA/TPA were treated over three weeks with either IgG control, anti-PD1 antibody monotherapy, 8 Gy of localized radiation, or a combination of anti-PD1 and 8 Gy of radiation followed by anti-PD1 therapy.Results: We found that while anti-PD1 therapy showed a trend toward slowed tumor growth compared to controls, this difference was not statistically significant (p= 0.0775), with most mice showing continued tumor progression. Preliminary histological analysis suggested that anti-PD1 treatment increased CD8+ T cell infiltration, and the addition of radiation further enhanced CD8+ responses but added greater variability. A pathologic review revealed that irradiated tumors were associated with fibroblastic spindle-like cell morphology.Conclusions: This animal model represents a potential preclinical model for studying CSCC with limited responses to immunotherapy to understand potential mechanisms of resistance.
背景/目的：非黑色素瘤皮肤癌，包括皮肤鳞状细胞癌（cSCC），是全球第五大常见癌症，发病率高，尽管死亡率较低，但总死亡人数超过黑色素瘤。虽然大多数cSCC病例可通过手术治疗，但局部晚期、转移性和高危cSCC肿瘤预后较差，复发率更高，需要多模式治疗。然而，关于皮肤鳞状细胞癌动物模型用于联合免疫疗法和放射治疗的数据有限。方法：在本研究中，使用DMBA/TPA自发生成的肿瘤在三周内接受IgG对照、抗PD1抗体单药治疗、8 Gy局部放射治疗，或抗PD1联合8 Gy放射治疗后继续抗PD1治疗。结果：我们发现，与对照组相比，抗PD1治疗显示出减缓肿瘤生长的趋势，但这一差异无统计学意义（p=0.0775），大多数小鼠的肿瘤继续进展。初步组织学分析表明，抗PD1治疗增加了CD8+ T细胞浸润，而联合放射治疗进一步增强了CD8+反应，但增加了更大的变异性。病理学检查显示，接受放射治疗的肿瘤与成纤维细胞样梭形细胞形态相关。结论：该动物模型代表了一种潜在的临床前模型，可用于研究对免疫疗法反应有限的cSCC，以了解潜在的耐药机制。
肿瘤(癌症)患者之家