Proton therapy (PT) is emerging as an effective and less toxic alternative to conventional X-ray-based photon therapy (XRT) for patients with advanced head and neck squamous cell carcinomas (HNSCCs) owing to its clustered dose deposition dosimetric characteristics. For optimal efficacy, cancer therapies, including PT, must elicit a robust anti-tumor response by effector and cytotoxic immune cells in the tumor microenvironment (TME). While tumor-derived exosomes contribute to immune cell suppression in the TME, information on the effects of PT on exosomes and anti-tumor immune responses in HNSCC is not known. In this study, we generated primary HNSCC cells from tumors resected from HNSCC patients, irradiated them with 5 Gy PT or XRT, and isolated exosomes from cell culture supernatants. HNSCC cells exposed to PT produced 75% fewer exosomes than XRT- and non-irradiated HNSCC cells. This effect persisted in proton-irradiated cells for up to five days. Furthermore, we observed that exosomes from proton-irradiated cells were identical in morphology and immunosuppressive effects (suppression of IFN-γ release by peripheral blood mononuclear cells) to those of photon-irradiated cells. Our results suggest that PT limits the suppressive effect of exosomes on cancer immune surveillance by reducing the production of exosomes that can inhibit immune cell function.
质子治疗（PT）凭借其剂量沉积集中的剂量学特性，正逐渐成为晚期头颈部鳞状细胞癌（HNSCC）患者传统X射线光子治疗（XRT）的一种有效且毒性更低的替代方案。为实现最佳疗效，包括质子治疗在内的癌症疗法必须通过肿瘤微环境（TME）中的效应细胞和细胞毒性免疫细胞引发强大的抗肿瘤反应。虽然肿瘤来源的外泌体在肿瘤微环境中会抑制免疫细胞功能，但质子治疗对头颈部鳞状细胞癌外泌体及抗肿瘤免疫反应的影响尚不明确。本研究从头颈部鳞状细胞癌患者切除的肿瘤组织中提取原代癌细胞，分别接受5 Gy质子治疗或X射线光子照射，并从细胞培养上清液中分离外泌体。结果显示，质子照射后的头颈部鳞状细胞癌细胞产生的外泌体数量较X射线照射组及未照射组减少75%，且该效应在质子照射后的细胞中可持续长达五天。此外，我们观察到质子照射细胞产生的外泌体在形态和免疫抑制功能（抑制外周血单核细胞释放干扰素-γ）方面与光子照射细胞产生的外泌体无显著差异。本研究结果表明，质子治疗通过减少具有免疫抑制功能的外泌体产生，从而限制外泌体对癌症免疫监视的抑制作用。
Proton Treatment Suppresses Exosome Production in Head and Neck Squamous Cell Carcinoma
肿瘤(癌症)患者之家