肿瘤细胞治疗研究
英文原题：Pathological complete response in microsatellite- stable gastric cancer with liver and bulky lymph node metastases after nivolumab-based chemotherapy and surgery: a case report.
本病例表明，即使在TMB水平较低的MSS胃癌中，异常高的PD-L1表达也可能预测对基于ICI的治疗产生显著应答。PD-L1 CPS可作为独立于TMB或微卫星不稳定状态的 critical 生物标志物。
伴有肝转移的胃癌通常预后较差，很少能够实现治愈性治疗。近年来，细胞毒性化疗与免疫检查点抑制剂（ICIs）的联合治疗显示出良好前景。然而，ICIs在治疗微卫星稳定（MSS）胃癌中的疗效仍存在争议。本文报道一例晚期MSS胃癌伴肝转移及巨大淋巴结转移的病例，采用S-1联合奥沙利铂（SOX）方案与nivolumab联合治疗，实现了病理完全缓解。病例介绍：一名64岁男性被诊断为胃腺癌，伴孤立性肝转移（S6）及巨大区域淋巴结转移。给予4个周期SOX联合nivolumab（360 mg，每3周一次）治疗。影像学显示肿瘤显著退缩，随后行手术治疗。患者接受了远端胃切除术联合D2淋巴结清扫及部分肝切除术。病理评估显示原发灶、淋巴结及肝脏中肿瘤完全退缩。肿瘤为MSS，Epstein-Barr病毒阴性，肿瘤突变负荷（TMB）低。免疫组化显示平均CD8+TIL（肿瘤浸润淋巴细胞）密度为59.5 ± 14.3个细胞/高倍视野，程序性死亡配体1（PD-L1）联合阳性评分（CPS）≥ 70%（克隆28-8），并伴有胚系TP53 p.R106C突变。
BACKGROUND: Gastric cancer with liver metastases is generally associated with poor prognosis, and curative treatment is rarely achieved. Recently, the combination of cytotoxic chemotherapy and immune checkpoint inhibitors (ICIs) has shown promise. However, the efficacy of ICIs in treating microsatellite-stable (MSS) gastric cancer remains controversial. Herein, we present a case of advanced MSS gastric cancer with liver and bulky lymph node metastases, in which combination therapy with S-1 plus oxaliplatin (SOX) and nivolumab led to a pathological complete response. CASE PRESENTATION: A 64-year-old man was diagnosed with gastric adenocarcinoma with a solitary liver metastasis (S6) and bulky regional lymph node metastasis. Four cycles of SOX and nivolumab (360 mg every 3 weeks) were administered. Imaging revealed marked tumor regression, and surgery was performed. The patient underwent distal gastrectomy with D2 lymphadenectomy and partial hepatectomy. Pathological evaluation revealed complete tumor regression in the primary lesion, lymph nodes, and liver. The tumor was MSS, Epstein-Barr virus-negative and had a low tumor mutational burden (TMB). Immunohistochemistry showed a mean CD8+ tumor-infiltrating lymphocyte density of 59.5 ± 14.3 cells per high-power field, a programmed death-ligand 1 (PD-L1) combined positive score (CPS) of ≥ 70% (clone 28-8), and a germline TP53 p.R106C mutation. CONCLUSION: This case illustrates that even in MSS gastric cancer with low TMB levels, exceptionally high PD-L1 expression may predict a profound response to ICI-based therapy. The PD-L1 CPS may serve as a critical biomarker independent of TMB or microsatellite-instability status.
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