Immunology Lab, Indian Institute of Advanced Research, Koba Institutional Area, Gandhinagar, Gujarat 382426, India.
Immunology Lab, Indian Institute of Advanced Research, Koba Institutional Area, Gandhinagar, Gujarat 382426, India.
Cytokine. 2022 Sep;157:155948. doi: 10.1016/j.cyto.2022.155948. Epub 2022 Jun 25.
Cellular communication mediated by cytokines is an important mechanism dictating immune responses, their cross talk and final immune output. Cytokines play a major role in dictating the immune outcome to cancer by regulating the events of development, differentiation and activation of innate immune cells. Cytokines are pleiotropic in nature, hence understanding their role individually or as member of network cytokines is critical to delineate their role in tumour immunity. Tumour systemically manipulates the immune system to evade and escape immune recognition for their uncontrollable growth and metastasis. The developing tumour comprise a large and diverse set of myeloid cells which are vulnerable to manipulation by the tumour-microenvironment. The innate immune cells of the monocytic lineage skew the fate of the adaptive immune cells and thus dictating cancer elimination or progression. Targeting cells at tumour cite is preposterous owing to their tight network, poor reach and abundance of immunosuppressive mechanisms. Monocytic lineage-derived cytokines (monokines) play crucial role in tumour regression or progression by either directly killing the tumour cells with TNFα or promoting its growth by TGFβ. In addition, the monokines like IL-12, IL-1β, IL-6, IL-10 and TGFβ direct the adaptive immune cells to secrete anti-tumour cytokines, TNFα, IFNγ, perforin and granzyme or pro-tumour cytokines, IL-10 and TGFβ. In this review, we elucidate the roles of monokines in dictating the fate of tumour by regulating responses at various stages of generation, differentiation and activation of immune cells along with the extensive cross talk. We have attempted to delineate the synergy and antagonism of major monokines among themselves or with tumour-derived or adaptive immune cytokines. The review provides an update on the possibilities of placing monokines to potential practical use as cytokine therapy against cancer.
细胞因子介导的细胞通讯是决定免疫反应、它们的串扰和最终免疫输出的重要机制。细胞因子通过调节先天免疫细胞的发育、分化和激活事件，在决定癌症的免疫结局方面发挥主要作用。细胞因子在本质上是多效的，因此，单独或作为网络细胞因子的成员理解它们的作用对于阐明它们在肿瘤免疫中的作用至关重要。肿瘤系统地操纵免疫系统，以逃避和逃脱免疫识别，从而实现其无法控制的生长和转移。正在发展的肿瘤包含大量和多样化的髓样细胞群体，这些细胞容易受到肿瘤微环境的操纵。单核细胞谱系的先天免疫细胞改变适应性免疫细胞的命运，从而决定癌症的消除或进展。由于肿瘤细胞的紧密网络、较差的可达性和丰富的免疫抑制机制，靶向肿瘤部位的细胞是荒谬的。单核细胞谱系衍生的细胞因子（单核因子）通过 TNFα 直接杀死肿瘤细胞或通过 TGFβ 促进其生长，在肿瘤消退或进展中发挥关键作用。此外，IL-12、IL-1β、IL-6、IL-10 和 TGFβ 等单核因子指导适应性免疫细胞分泌抗肿瘤细胞因子 TNFα、IFNγ、穿孔素和颗粒酶，或促肿瘤细胞因子 IL-10 和 TGFβ。在这篇综述中，我们通过调节免疫细胞在产生、分化和激活的各个阶段的反应，阐明单核因子通过调节免疫细胞在产生、分化和激活的各个阶段的反应来决定肿瘤命运的作用，以及广泛的串扰。我们试图描述主要单核因子之间、与肿瘤衍生或适应性免疫细胞因子之间的协同作用和拮抗作用。该综述提供了关于将单核因子作为细胞因子治疗癌症的潜在实际用途的最新信息。
