BackgroundRadiation therapy combined with immune checkpoint inhibitors (ICIs) has recently turned into an appealing and promising approach to enhance the anti-tumor immunity and efficacy of immunological drugs in many tumors. Abscopal effect induced by radiation is a phenomenon that often leads to an efficient immunity response. In this study, we investigated whether the combination of the immunogenic effects derived from radiotherapy sequential ICIs-based therapy could increase the incidence of abscopal effects, and improve the survival rates.Case presentationWe described a clinical case regarding a 35-year-old male patient who was admitted to our hospital with a diagnosis of adenocarcinoma of the sigmoid colon and synchronous multiple liver metastases following a surgical resection. The molecular pathological examination showed immune-desert phenotype and proficient mismatch repair (pMMR). The patient was treated with adjuvant chemotherapy after surgery, however, after 7 months, multiple metastasis in the pelvic lymph nodes were diagnosed. Unfortunately, the tumor progressed despite multiple cycles of chemotherapy combined with cetuximab or bevacizumab. Within the follow-up treatment, the patient was administered with only 50Gy/25F of radiation dose to treat the anastomotic lesions. Subsequently, mono-sindilizumab was used as systemic therapy, leading to a rapid reduction of all pelvic lesions and complete clinical remission. So far, the patient survived for more than 20 months under continuous mono-sindilizumab treatment and is still in complete remission.ConclusionA localized radiotherapy combined with a sindilizumab-based systemic therapy may overcome the immune resistance of pMMR metastatic colorectal cancer (mCRC), thus obtaining greater efficacy of the therapy. Its mechanism may be related to the abscopal effect obtained by the synergistic use of radiation and sindilizumab, which should be further investigated in the future.

中文翻译：

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放射序贯单免疫疗法引发的远隔效应导致 PMMR 乙状结肠癌完全缓解

背景放射治疗联合免疫检查点抑制剂 (ICI) 最近已成为一种有吸引力和有前途的方法，可以增强免疫药物在许多肿瘤中的抗肿瘤免疫力和疗效。辐射引起的远隔效应是一种经常导致有效免疫反应的现象。在这项研究中，我们调查了放疗序贯基于 ICI 的治疗所产生的免疫原性效应的组合是否可以增加远隔效应的发生率，并提高生存率。病例介绍我们描述了一个关于一名 35 岁男性患者的临床病例他因乙状结肠腺癌和手术切除后同步多发性肝转移而入院。分子病理学检查显示免疫荒漠表型和熟练的错配修复（pMMR）。患者术后接受辅助化疗，7个月后诊断为盆腔淋巴结多发转移。不幸的是，尽管进行了多个周期的化疗联合西妥昔单抗或贝伐珠单抗，但肿瘤仍在进展。在后续治疗中，患者仅接受了 50Gy/25F 的辐射剂量来治疗吻合口病变。随后，mono-sindilizumab 被用作全身治疗，导致所有盆腔病变迅速减少并完全临床缓解。迄今为止，患者在持续的单辛迪珠单抗治疗下存活了20多个月，目前仍处于完全缓解状态。结论局部放疗联合以辛迪珠单抗为基础的全身治疗可克服pMMR转移性结直肠癌（mCRC）的免疫耐药性，从而获得更大疗效。其作用机制可能与放疗与辛地珠单抗协同使用获得远隔效应有关，有待进一步研究。