Immune checkpoint blockade (ICB) therapy is used to treat a wide range of cancers; however, some patients are at risk of developing treatment resistance and/or immune-related adverse events (irAEs). Thus, there is a great need for the identification of reliable predictive biomarkers for response and toxicity. The cytokine MIF (macrophage migration inhibitory factor) and its cognate receptor CD74 are intimately connected with cancer progression and have previously been proposed as prognostic biomarkers for patient outcome in various cancers, including solid tumors such as malignant melanoma. Here, we assess their potential as predictive biomarkers for response to ICB therapy and irAE development. We provide a brief overview of their function and roles in the context of cancer and autoimmune disease. We also review the evidence showing that MIF and CD74 may be of use as predictive biomarkers of patient response to ICB therapy and irAE development. We also highlight that careful consideration is required when assessing the potential of serum MIF levels as a biomarker due to its reported circadian expression in human plasma. Finally, we suggest future directions for the establishment of MIF and CD74 as predictive biomarkers for ICB therapy and irAE development to guide further research in this field.
免疫检查点阻断疗法被广泛应用于多种癌症的治疗，然而部分患者存在产生治疗耐药性和/或免疫相关不良事件的风险。因此，亟需寻找能够可靠预测疗效与毒性的生物标志物。细胞因子巨噬细胞移动抑制因子及其同源受体CD74与癌症进展密切相关，先前研究已提出其可作为包括恶性黑色素瘤在内的多种实体瘤患者预后的生物标志物。本文旨在评估其作为预测免疫检查点阻断疗法疗效及免疫相关不良事件发生风险的潜在生物标志物价值。我们简要概述了它们在癌症和自身免疫性疾病背景下的功能与作用，并综述了相关证据表明MIF和CD74可能作为预测患者对免疫检查点阻断疗法反应及免疫相关不良事件发展的生物标志物。需要特别指出的是，由于已有研究报道MIF在人血浆中具有昼夜节律性表达特征，在评估血清MIF水平作为生物标志物的潜力时需要审慎考量。最后，我们提出了将MIF和CD74确立为免疫检查点阻断疗法及免疫相关不良事件预测性生物标志物的未来研究方向，以推动该领域的进一步研究。
MIF and CD74 as Emerging Biomarkers for Immune Checkpoint Blockade Therapy
肿瘤(癌症)患者之家