Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Ministry of Education (MOE) Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, Jinan University, Guangzhou, China.
Front Immunol. 2022 Sep 2;13:981527. doi: 10.3389/fimmu.2022.981527. eCollection 2022.
Traditionally, patients with microsatellite stability (MSS)/microsatellite instability-Low (MSI-L)/proficient mismatch repair (p-MMR) metastatic colorectal cancer (mCRC) have had poor benefit from immunotherapy. Therefore, how to enhance the response of immunotherapy is still a challenge for MSS/MSI-L/p-MMR CRC patient.
We report a special case of a rectal cancer patient with programmed death-ligand 1 (PD-L1) negative expression, MSI-L/p-MMR, tumor mutational burden-low (TMB-L) and liver metastases, who partial response (PR) to immunotherapy after systemic therapy failure including chemotherapy, anti-angiogenesis therapy and stereotactic body radiation-therapy (SBRT). The computed tomography (CT) results showed that among three liver metastases had been reduction or disappearance after Tislelizumab treatment for three times. Besides, the carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199) decrease and maintained at a low level for 3 months. The progression-free survival (PFS) of patient has exceeded 3 months.
This case indicates that the patient with MSI-L/p-MMR mCRC can respond to anti-PD-1 immunotherapy after systemic therapy. And the SBRT (targeting liver metastases) may a method for increase-sensitivity of immunotherapy in CRC patients with MSI-L/p-MMR.
传统上,微卫星稳定性(MSS)/微卫星不稳定性低(MSI-L)/熟练错配修复(p-MMR)转移性结直肠癌(mCRC)患者从免疫治疗中获益不佳。因此,如何提高免疫治疗的反应率仍是 MSS/MSI-L/p-MMR CRC 患者面临的挑战。
我们报告了一例特殊的直肠 MSI-L/p-MMR、肿瘤突变负担低(TMB-L)和肝转移的 PD-L1 阴性表达的结直肠癌患者,在包括化疗、抗血管生成治疗和立体定向体放射治疗(SBRT)在内的全身治疗失败后对免疫治疗有部分缓解(PR)。计算机断层扫描(CT)结果显示,在Tislelizumab 治疗三次后,其中三个肝转移灶已经减少或消失。此外,癌胚抗原(CEA)和碳水化合物抗原 199(CA199)下降并在 3 个月内保持在低水平。患者的无进展生存期(PFS)已超过 3 个月。
本病例表明,MSI-L/p-MMR mCRC 患者在全身治疗后可以对抗 PD-1 免疫治疗有反应。SBRT(针对肝转移灶)可能是提高 MSI-L/p-MMR 结直肠癌患者免疫治疗敏感性的一种方法。