Role of chemokine systems in cancer and inflammatory diseases

Abstract

Chemokines are a large family of small secreted proteins that have fundamental roles in organ development, normal physiology, and immune responses upon binding to their corresponding receptors. The primary functions of chemokines are to coordinate and recruit immune cells to and from tissues and to participate in regulating interactions between immune cells. In addition to the generally recognized antimicrobial immunity, the chemokine/chemokine receptor axis also exerts a tumorigenic function in many different cancer models and is involved in the formation of immunosuppressive and protective tumor microenvironment (TME), making them potential prognostic markers for various hematologic and solid tumors. In fact, apart from its vital role in tumors, almost all inflammatory diseases involve chemokines and their receptors in one way or another. Modulating the expression of chemokines and/or their corresponding receptors on tumor cells or immune cells provides the basis for the exploitation of new drugs for clinical evaluation in the treatment of related diseases. Here, we summarize recent advances of chemokine systems in protumor and antitumor immune responses and discuss the prevailing understanding of how the chemokine system operates in inflammatory diseases. In this review, we also emphatically highlight the complexity of the chemokine system and explore its potential to guide the treatment of cancer and inflammatory diseases.

Combined mitoxantrone and anti-TGFβ treatment with PD-1 blockade enhances antitumor immunity by remodelling the tumor immune landscape in neuroblastoma

“…In addition to promoting recruitment and effector function of tumor-specific CD8 + T cells, these chemokines are also able to enrich the TME of functional DC and NK cells, two key immune components associated with improved survival of both adult and pediatric cancer patients [ 5 ]. Particularly important is the increase of CCL5, produced by CD8 + T cells, NK cells and innate lymphoid cells, that is crucial for recruitment of cDC1s, macrophages and Treg cells in the TME [ 85 ]; CXCL9, CXCL10 and CXCL16, produced by DCs and macrophages, that induce the recruitment and activation of NK cells, NKT cells and CD8 + T cells [ 5 , 86 – 88 ]; CCL21, that significantly increase the proportion of T cells, NK cells and DCs within the tumor [ 89 ]; CD40 and FLT3L, produced by intratumoral NK cells, which supports the viability and functions of cDC1s within the TME by promoting their local differentiation from precursor cells [ 19 , 90 ]. Interestingly, CXCL9 expression by cDCs has been previously described to mediate the clustering of DC-T cells within lymph nodes [ 91 ], and since interaction between these two immune cell populations is quite rare in tumors [ 22 , 92 ], it is possible that increased CXCL9 expression by facilitating these interactions may promote T-cell effector function.…”

Assessing the influence of small structural modifications in simple DNA-based nanostructures on their role as drug nanocarriers

“…However, almost no significant differences in cytotoxicity are observed in DOX-loaded DNS in HeLa cells, indicating the importance of the type of cell in the design of a particular nanostructure as a drug carrier. Although there is a lack of standardized reported results in the DNA nanotechnology field, 35,36 we can conclude that, overall, our simple design DNS show outstanding properties regarding stability in free-Mg 2+ physiological buffers and resistance against serum degradation compared to complex DNA origamis. For instance, a reported icosahedral origami does show a high amount of degradation after 6 h incubation in FBS-containing media.…”

Piper nigrum extract retards tumor growth by reducing tumor-promoted cytokines/chemokines and modulating immune cells in blood circulation

“…These results suggest that PFPE effectively reduced chemokines/cytokines associated with in ammation and immune tra cking. After 31 days of PFPE feeding, PFPE inhibits six more cytokine/chemokine than point 1, which is related to supporting tumor cell proliferation and progression and the development of adaptive immunity [29]. These results might be cancer has occurred but were not detectable.…”