The paradoxical role of cytokines and chemokines at the tumor microenvironment: a comprehensive review

Abstract

Tumor progression and eradication have long piqued the scientific community's interest. Recent discoveries about the role of chemokines and cytokines in these processes have fueled renewed interest in related research. These roles are frequently viewed as contentious due to their ability to both suppress and promote cancer progression. As a result, this review critically appraised existing literature to discuss the unique roles of cytokines and chemokines in the tumor microenvironment, as well as the existing challenges and future opportunities for exploiting these roles to develop novel and targeted treatments. While these modulatory molecules play an important role in tumor suppression via enhanced cancer-cell identification by cytotoxic effector cells and directly recruiting immunological effector cells and stromal cells in the TME, we observed that they also promote tumor proliferation. Many cytokines, including GM-CSF, IL-7, IL-12, IL-15, IL-18, and IL-21, have entered clinical trials for people with advanced cancer, while the FDA has approved interferon-alpha and IL-2. Nonetheless, low efficacy and dose-limiting toxicity limit these agents' full potential. Conversely, Chemokines have tremendous potential for increasing cancer immune-cell penetration of the tumor microenvironment and promoting beneficial immunological interactions. When chemokines are combined with cytokines, they activate lymphocytes, producing IL-2, CD80, and IL-12, all of which have a strong anticancer effect. This phenomenon opens the door to the development of effective anticancer combination therapies, such as therapies that can reverse cancer escape, and chemotaxis of immunosuppressive cells like Tregs, MDSCs, and TAMs.

Role of SYT11 in human pan-cancer using comprehensive approaches

“…M1 macrophages are tumor resistant macrophages as they can identify and kill cancer cells. In contrast to M1 macrophages, peri- and intra-tumoral M2 macrophages promote tumor progression through involvement in migration, invasion, angiogenesis, neovascularization, stromal activation, and extracellular matrix remodeling [ 49 , 50 ]. Collectively, these findings suggest that abnormal SYT11 expression plays a role in the relationship between immune subsets and anti-tumor immunity.…”

Deciphering Regulatory T-Cell Dynamics in Cancer Immunotherapy: Mechanisms, Implications, and Therapeutic Innovations

“…The cytokine gradients generated by tumor and immune cells attract nTreg cells to the TME. 35 Abdul-Rahman et al 36 investigate into the complex and dual roles of cytokines and chemokines within the TME, elucidating their paradoxical nature in both promoting and inhibiting cancer progression. The review meticulously explores how these molecules facilitate tumor suppression by enhancing the recruitment and function of cytotoxic effector cells, stromal cells, and immunological effectors in the TME, while also acknowledging their role in supporting tumor proliferation and survival.…”

Modulation of adipose-derived stem cell behavior by prostate pathology-associated plasma: insights from in vitro exposure

“…These cytokines, along with chemokines, play a crucial role in modulating tumor cell behavior and immune response, contributing to the complexity of the TME 21 . The expression of these molecules increases concomitantly with tumor progression and contributes to the promotion of metastasis 22 . The clinical significance of ADSCs in prostate cancer research lies in their ability to modulate the TME and thus influence the viability of tumor cells 23 – 25 .…”