RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:SOX chemotherapy with anti-PD-1 and iNKT cell immunotherapies for stage IV gastric adenocarcinoma with liver metastases: A case report.
SOX chemotherapy with anti-PD-1 and iNKT cell immunotherapies for stage IV gastric adenocarcinoma with liver metastases: A case report.
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胃癌(GC)是全球第四大常见癌症,总体5年生存率约为20%。尽管手术联合化疗和免疫治疗的多模式治疗已被证明可提高生存率,但在伴有肝转移的晚期GC患者中,病理完全缓解(pCR)较为罕见。临床前研究和临床试验已证实恒定自然杀伤T(iNKT)细胞在包括GC在内的多种恶性肿瘤中具有抗肿瘤疗效。
然而,由化疗、抗程序性细胞死亡-1(PD-1)治疗和iNKT细胞免疫治疗组成多模式治疗尚未在GC患者中报道。本病例报告描述了一名60岁出头的患者,诊断为晚期IVB期(T1N1M1)胃贲门腺癌伴肝转移,接受了由SOX化疗、抗程序性细胞死亡-1(PD-1)治疗和iNKT细胞免疫治疗组成的多模式治疗,随后进行手术切除。在六个周期的SOX化疗和iNKT细胞免疫治疗以及四个周期的抗PD-1治疗后,原发肿瘤和转移病灶的肿瘤面积均显著缩小。这种联合治疗使一个显著巨大的、不可切除的肝转移灶转变为可切除肿瘤,患者接受了全胃切除术联合D2淋巴结清扫和肝转移灶切除术。随后的病理检查在原发部位和肝转移病灶中均未检测到癌细胞,支持该治疗很可能达到了pCR。据我们所知,本报告代表了首例转移性胃癌患者在接受六个月多模式治疗后达到pCR的病例,因此支持SOX化疗、抗PD-1治疗和iNKT细胞免疫治疗联合策略可能对治疗、并可能治愈晚期胃腺癌患者有效。
Gastric cancer (GC) is the fourth most common cancer worldwide, with overall 5-year survival rate of approximate 20%. Although multimodal treatments that combine surgery with chemotherapy and immunotherapy have been shown to improve survival, pathological complete response (pCR) is rare in advanced GC patients with liver metastases. Pre-clinical studies and clinical trials have demonstrated the antitumor efficacy of invariant natural killer T (iNKT) cells in various malignancies, including GC. While multimodal therapy comprised of chemotherapy, anti-programmed cell death-1 (PD-1) therapy, and iNKT cell immunotherapy have not been reported in GC patients. This case report describes the treatment of an early 60s patient diagnosed with advanced stage IVB (T1N1M1) adenocarcinomas of gastric cardia with liver metastases who received multimodal therapy comprised of SOX chemotherapy, anti-programmed cell death-1 (PD-1) therapy, and iNKT cell immunotherapy followed by surgical resection.
Dramatic decreases in tumor area were observed in both the primary tumor and metastatic lesions following six cycles of SOX chemotherapy and iNKT cell immunotherapy, and four cycles of anti-PD-1 therapy. This combined treatment resulted in the transformation of a remarkably large, unresectable liver metastases into a resectable tumor, and the patient received total gastrectomy with D2 lymph node dissection and liver metastasectomy.
Subsequent pathological examination detected no cancer cells in either the primary site or liver metastatic lesions, supporting the likelihood that this treatment achieved pCR. To our knowledge, this report represents the first case of a metastatic gastric cancer patient displaying pCR after six months of multimodal therapy, thus supporting that a SOX chemotherapy, anti-PD-1 therapy, and iNKT cell immunotherapy combination strategy may be effective for treating, and potentially curing, patients with advanced gastric adenocarcinoma.
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