NSCLC, the most common type of lung cancer, is often diagnosed late due to minimal early symptoms. Its high risk of recurrence or metastasis post-chemotherapy makes DC-based immunotherapy a promising strategy, offering targeted cancer destruction, low side effects, memory formation, and overcoming the immune evasive ability of cancers. However, the limited response to DCs pulsed with single antigens remains a significant challenge. To overcome this, we enhanced DC antigen presentation by pulsing with TAAs. Our study focused on enhancing DC-mediated immune response specificity and intensity by combinatorial pulsing of TAAs, selected for their prevalence in NSCLC. We selected four types of TAAs expressed in NSCLC and pulsed DCs with the optimal combination. Next, we administered TAAs-pulsed DCs into the LLC1 mouse model to evaluate their anti-tumor efficacy. Our results showed that TAAs-pulsed DCs significantly reduced tumor size and promoted apoptosis in tumor tissue. Moreover, TAAs-pulsed DCs significantly increased total T cells in the spleen compared to the unpulsed DCs. Additionally, in vitro stimulation of splenocytes from the TAAs-pulsed DCs showed notable T-cell proliferation and increased IFN-γ secretion. Our findings demonstrate the potential of multiple TAA pulsing to enhance the antigen-presenting capacity of DCs, thereby strengthening the immune response against tumors.
非小细胞肺癌作为最常见的肺癌类型,由于早期症状隐匿,常被晚期确诊。其在化疗后复发或转移的高风险使得基于树突状细胞的免疫疗法成为一种前景广阔的治疗策略,该疗法具有靶向杀伤肿瘤、副作用低、可形成免疫记忆并能克服肿瘤免疫逃逸能力等优势。然而,单抗原脉冲的树突状细胞应答有限仍是重大挑战。为突破此局限,我们通过肿瘤相关抗原脉冲处理来增强树突状细胞的抗原呈递能力。本研究聚焦于通过组合脉冲在非小细胞肺癌中高表达的肿瘤相关抗原,以增强树突状细胞介导的免疫反应特异性与强度。我们筛选出四种在非小细胞肺癌中表达的肿瘤相关抗原,并以最优组合脉冲处理树突状细胞。随后将肿瘤相关抗原脉冲的树突状细胞注入LLC1小鼠模型,评估其抗肿瘤效果。结果显示,肿瘤相关抗原脉冲的树突状细胞能显著缩小肿瘤体积并促进肿瘤组织凋亡。与未脉冲组相比,该处理显著增加了脾脏总T细胞数量。此外,体外刺激肿瘤相关抗原脉冲树突状细胞组的脾淋巴细胞显示出显著的T细胞增殖及干扰素-γ分泌增加。我们的研究证实,多重肿瘤相关抗原脉冲能有效增强树突状细胞的抗原呈递能力,从而强化机体抗肿瘤免疫应答。