Díaz-Tejedor Andrea, Lorenzo-Mohamed Mauro, Puig Noemí, García-Sanz Ramón, Mateos María-Victoria, Garayoa Mercedes, Paíno Teresa
Centro de Investigación del Cáncer-IBMCC (CSIC-Universidad de Salamanca), Complejo Asistencial Universitario de Salamanca-IBSAL, Department of Hematology, 37007 Salamanca, Spain.
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC, CB16/12/00233), Instituto de Salud Carlos III, 37007 Salamanca, Spain.
Cancers (Basel). 2021 Mar 17;13(6):1353. doi: 10.3390/cancers13061353.
Immunosuppression is a common feature of multiple myeloma (MM) patients and has been associated with disease evolution from its precursor stages. MM cells promote immunosuppressive effects due to both the secretion of soluble factors, which inhibit the function of immune effector cells, and the recruitment of immunosuppressive populations. Alterations in the expression of surface molecules are also responsible for immunosuppression. In this scenario, immunotherapy, as is the case of immunotherapeutic monoclonal antibodies (mAbs), aims to boost the immune system against tumor cells. In fact, mAbs exert part of their cytotoxic effects through different cellular and soluble immune components and, therefore, patients' immunosuppressive status could reduce their efficacy. Here, we will expose the alterations observed in symptomatic MM, as compared to its precursor stages and healthy subjects, in the main immune populations, especially the inhibition of effector cells and the activation of immunosuppressive populations. Additionally, we will revise the mechanisms responsible for all these alterations, including the interplay between MM cells and immune cells and the interactions among immune cells themselves. We will also summarize the main mechanisms of action of the four mAbs approved so far for the treatment of MM. Finally, we will discuss the potential immune-stimulating effects of non-immunotherapeutic drugs, which could enhance the efficacy of immunotherapeutic treatments.
免疫抑制是多发性骨髓瘤（MM）患者的一个常见特征，并且与疾病从其前驱阶段开始的演变相关。MM细胞促进免疫抑制作用，这是由于可溶性因子的分泌（其抑制免疫效应细胞的功能）以及免疫抑制群体的募集。表面分子表达的改变也导致免疫抑制。在这种情况下，免疫疗法，如免疫治疗性单克隆抗体（mAb），旨在增强免疫系统对抗肿瘤细胞。事实上，mAb通过不同的细胞和可溶性免疫成分发挥其部分细胞毒性作用，因此，患者的免疫抑制状态可能会降低其疗效。在这里，我们将阐述与前驱阶段和健康受试者相比，在有症状的MM中主要免疫群体所观察到的改变，特别是效应细胞的抑制和免疫抑制群体的激活。此外，我们将探讨导致所有这些改变的机制，包括MM细胞与免疫细胞之间的相互作用以及免疫细胞自身之间的相互作用。我们还将总结目前已批准用于治疗MM的四种mAb的主要作用机制。最后，我们将讨论非免疫治疗药物潜在的免疫刺激作用，其可能会提高免疫治疗的疗效。
