David Geffen School of Medicine at UCLA, Santa Monica, CA.
UT MD Anderson Cancer Center, Houston, TX.
Am Soc Clin Oncol Educ Book. 2023 Jun;43:e389072. doi: 10.1200/EDBK_389072.
Immunotherapy has only had a modest impact on the treatment of advanced GI malignancies. Microsatellite-stable colorectal cancer and pancreatic adenocarcinoma, the most common GI tumors, have not benefited from treatment with standard immune checkpoint inhibitors. With this huge unmet need, multiple approaches are being tried to overcome barriers to better anticancer outcomes. This article reviews a number of novel approaches to immunotherapy for these tumors. These include the use of novel checkpoint inhibitors such as a modified anti-cytotoxic T lymphocyte-associated antigen-4 antibody and antibodies to lymphocyte-activation gene 3, T cell immunoreceptor with immunoglobulin and ITIM domains, T-cell immunoglobulin-3, CD47, and combinations with signal transduction inhibitors. We will discuss other trials that aim to elicit an antitumor T-cell response using cancer vaccines and oncolytic viruses. Finally, we review attempts to replicate in GI cancers the frequent and durable responses seen in hematologic malignancies with immune cell therapies.
免疫疗法仅对晚期胃肠道恶性肿瘤的治疗有一定影响。微卫星稳定的结直肠癌和胰腺腺癌是最常见的胃肠道肿瘤，并未从标准免疫检查点抑制剂治疗中获益。鉴于这种巨大的未满足需求，正在尝试多种方法来克服癌症治疗效果的障碍。本文综述了这些肿瘤的一些新的免疫治疗方法。这些方法包括使用新型检查点抑制剂，如改良的抗细胞毒性 T 淋巴细胞相关抗原 4 抗体和淋巴细胞激活基因 3 抗体、具有免疫球蛋白和 ITIM 结构域的 T 细胞免疫受体、T 细胞免疫球蛋白-3、CD47 以及与信号转导抑制剂的联合用药。我们将讨论其他旨在使用癌症疫苗和溶瘤病毒引发抗肿瘤 T 细胞反应的试验。最后，我们回顾了尝试用免疫细胞疗法在胃肠道癌症中复制在血液恶性肿瘤中常见且持久的反应的尝试。
