Immunoglobulin (Ig) G1 antibodies stimulate antibody-dependent cell-mediated cytotoxicity (ADCC). Cetuximab, an IgG1 isotype monoclonal antibody, is a standard-of-care treatment for locally advanced and recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) and metastatic colorectal cancer (CRC). Here we review evidence regarding the clinical relevance of cetuximab-mediated ADCC and other immune functions and provide a biological rationale concerning why this property positions cetuximab as an ideal partner for immune checkpoint inhibitors (ICIs) and other emerging immunotherapies. We performed a nonsystematic review of available preclinical and clinical data involving cetuximab-mediated immune activity and combination approaches of cetuximab with other immunotherapies, including ICIs, in SCCHN and CRC. Indeed, cetuximab mediates ADCC activity in the intratumoral space and primes adaptive and innate cellular immunity. However, counterregulatory mechanisms may lead to immunosuppressive feedback loops. Accordingly, there is a strong rationale for combining ICIs with cetuximab for the treatment of advanced tumors, as targeting CTLA-4, PD-1, and PD-L1 can ostensibly overcome these immunosuppressive counter-mechanisms in the tumor microenvironment. Moreover, combining ICIs (or other immunotherapies) with cetuximab is a promising strategy for boosting immune response and enhancing response rates and durability of response. Cetuximab immune activity—including, but not limited to, ADCC—provides a strong rationale for its combination with ICIs or other immunotherapies to synergistically and fully mobilize the adaptive and innate immunity against tumor cells. Ongoing prospective studies will evaluate the clinical effect of these combination regimens and their immune effect in CRC and SCCHN and in other indications.

免疫球蛋白（Ig）G1抗体刺激抗体依赖性细胞介导的细胞毒性（ADCC）。西妥昔单抗是一种IgG1同型单克隆抗体，是用于局部晚期和复发和/或转移性头颈部鳞状细胞癌（SCCHN）和转移性结直肠癌（CRC）的护理标准治疗方法。在这里，我们回顾了有关西妥昔单抗介导的ADCC和其他免疫功能的临床相关性的证据，并提供了有关此特性为何将西妥昔单抗定位为免疫检查点抑制剂（ICI）和其他新兴免疫疗法的理想伴侣的生物学原理。我们对涉及西妥昔单抗介导的免疫活性以及西妥昔单抗与其他免疫疗法（包括ICI）在SCCHN和CRC中的结合方法的可用临床前和临床数据进行了非系统性综述。确实，西妥昔单抗介导肿瘤内空间中的ADCC活性并引发适应性和先天性细胞免疫。但是，反调节机制可能会导致免疫抑制反馈回路。因此，将ICI与西妥昔单抗联合用于治疗晚期肿瘤是有很强的理由的，因为靶向CTLA-4，PD-1和PD-L1可以表面上克服肿瘤微环境中的这些免疫抑制性反机制。此外，将ICI（或其他免疫疗法）与西妥昔单抗联合使用是提高免疫应答，提高应答率和应答持久性的一种有前途的策略。西妥昔单抗的免疫活性（包括但不限于ADCC）为其与ICI或其他免疫疗法的结合提供了强有力的原理，以协同并充分调动针对肿瘤细胞的适应性免疫和先天免疫。