肿瘤异质性的存在已被广泛认可;然而,尚未报道同一患者多个肿瘤结节中抗肿瘤反应的异质性。Sintilimab,一种抗程序性细胞死亡受体-1(PD-1)的单克隆抗体,用于治疗不可切除的肝细胞癌(HCC)患者。在本研究中,我们报道了一例复发性HCC伴肺转移的治疗异质性病例。一名57岁的女性患者被诊断为HCC并接受了根治性肝切除术。一年半之后,成像扫描发现肺部有多个转移性肿瘤,伴随着甲胎蛋白(AFP)水平的升高。然后患者开始接受sintilimab。在sintilimab治疗后的前6个月,所有的转移性结节逐渐消退并最终消失,除了一个结节,在接下来的3个月中保持稳定。最后,患者接受了肺叶切除术以切除剩余的结节。此后,随访显示AFP水平降至正常,影像学扫描显示无复发迹象,确认患者表现出临床完全缓解。病理评估显示,在原发肿瘤部位,肿瘤包括中度分化的HCC,有少量浸润的细胞毒性T细胞和阴性的PD-L1表达。在转移部位,结节由低分化HCC组成,细胞毒性T细胞浸润,肿瘤内部细胞很少,在肿瘤的某些区域表达PD-L1。抗PD-1治疗后,原发性和复发性HCC病变中PD-L1表达和细胞毒性T细胞浸润的动态变化。该病例显示了同一患者转移结节中肿瘤微环境和随后的抗肿瘤反应的异质性,并揭示了综合治疗在癌症治疗中的重要性。
The existence of tumor heterogeneity is widely recognized; however, heterogeneity of the antitumor response in multiple tumor nodules in the same patient has not been reported. Sintilimab, a monoclonal antiprogrammed cell death receptor-1 (PD-1) antibody, was used to treat patients with unresectable hepatocellular carcinoma (HCC). In the present study, we report a
case of therapeutic heterogeneity in relapsed HCC with lung metastases. A 57-year-old female patient was diagnosed with HCC and underwent radical hepatectomy. One and a half years later, imaging scans found multiple metastatic tumors in the lung, which were accompanied by an increased α-fetoprotein (AFP) level. The patient then started to receive sintilimab. In the first 6 months after sintilimab treatment, all the metastatic nodules regressed gradually and ultimately disappeared, except for one nodule, which remained stable in the following 3 months. Finally, the patient underwent pulmonary lobectomy to remove the remaining nodule. Thereafter, follow-up visits showed the AFP level decreased to normal and imaging scans showed no signs of recurrence, confirming that the patient exhibited a clinically complete response. Pathological assessments showed that in the primary tumor site, the tumor comprised moderately differentiated HCC with a few infiltrated cytotoxic T cells and negative PD-L1 expression. While in the metastatic site, the nodule was composed of poorly differentiated HCC with cytotoxic T-cell infiltration with few cells inside the tumor and expressed PD-L1 in some areas of the tumor. There were dynamic alterations of PD-L1 expression and cytotoxic T-cell infiltration in the primary and relapsed HCC lesions after anti-PD-1 treatment. This
case presented the heterogeneities of both the tumor microenvironment and the following antitumor response among the metastatic nodules in the same patient and revealed the importance of comprehensive therapy in cancer treatment.