Wang Han, Qian You-Wen, Dong Hui, Cong Wen-Ming
Department of Pathology, Shanghai Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China.
Hepatobiliary Surg Nutr. 2024 Jun 1;13(3):472-493. doi: 10.21037/hbsn-22-527. Epub 2023 Apr 4.
Immune checkpoint inhibitor (ICI)-based therapy has achieved impressive success in various cancer types. Several ICIs have been unprecedentedly approved as the treatment regimens for advanced hepatocellular carcinoma (HCC) in recent decade. Meanwhile, numerous clinical trials are being performed to exploit more ICIs into initially unresectable HCC and postoperative HCC to expectantly induce adequate tumor downstaging for further resection or implement adjuvant treatment for relapse-free survival, respectively. In this review, we aim to summarize some pragmatic histomorphologic, immunohistochemical, and molecular pathologic parameters which promisingly indicate the response of neoadjuvant/conversion ICI-related therapy and predict the efficacy of adjuvant/therapeutic ICI-related therapy for HCC.
We searched PubMed using the terms hepatocellular carcinoma, immunotherapy, immune checkpoint inhibitor, immune checkpoint blockade, conversion therapy, neoadjuvant therapy, adjuvant therapy, biomarker, pathologic evaluation, pathologic assessment till February 2023.
Although there is no consensus regarding the pathologic evaluation of relevant HCC specimens, it is encouraging that a few of studies have concentrated on this field, and moreover, the methods and parameters noted on other cancer types are also worthy of reference. For the pathologic assessment of HCC specimens underwent immunotherapy, a suitable sampling scheme, identifying immunotherapy-related pathologic response, and quantification of pathologic response rate should be emphasized. For the patients of HCC who are scheduled to receive immunotherapy, tumor-infiltrating lymphocyte, intratumoral tertiary lymphoid structure, programmed cell death ligand 1, , microsatellite instability and mismatch repair, tumor mutational burden and tumor neoantigen, as well as some other signaling pathways are the potential predictive biomarkers of treatment response of ICI.
The management of HCC in the era of immunotherapy arises a brand-new pathological challenge that is to provide an immunotherapy-related diagnostic report. Albeit many related researches are preclinical or insufficient, they may tremendously alter the immunotherapy strategy of HCC in future.
基于免疫检查点抑制剂（ICI）的疗法在多种癌症类型中取得了令人瞩目的成功。近十年来，几种ICI已被史无前例地批准用于晚期肝细胞癌（HCC）的治疗方案。与此同时，众多临床试验正在进行，旨在将更多ICI应用于初始不可切除的HCC和术后HCC，以期分别诱导足够的肿瘤降期以便进一步切除，或实施辅助治疗以实现无复发生存。在本综述中，我们旨在总结一些实用的组织形态学、免疫组化和分子病理参数，这些参数有望表明新辅助/转化ICI相关疗法的反应，并预测辅助/治疗性ICI相关疗法对HCC的疗效。
我们在PubMed上使用搜索词“肝细胞癌”“免疫疗法”“免疫检查点抑制剂”“免疫检查点阻断”“转化疗法”“新辅助疗法”“辅助疗法”“生物标志物”“病理评估”“病理评价”进行搜索，直至2023年2月。
尽管对于相关HCC标本的病理评估尚无共识，但令人鼓舞的是，已有一些研究关注这一领域，此外，其他癌症类型中提及的方法和参数也值得参考。对于接受免疫治疗的HCC标本的病理评估，应强调合适的采样方案、识别免疫治疗相关的病理反应以及病理反应率的量化。对于计划接受免疫治疗的HCC患者，肿瘤浸润淋巴细胞、瘤内三级淋巴结构、程序性细胞死亡配体1、微卫星不稳定性和错配修复、肿瘤突变负荷和肿瘤新抗原，以及一些其他信号通路是ICI治疗反应的潜在预测生物标志物。
免疫治疗时代HCC的管理带来了全新的病理挑战，即提供一份与免疫治疗相关的诊断报告。尽管许多相关研究是临床前研究或不够充分，但它们可能在未来极大地改变HCC的免疫治疗策略。
