Cytokines in Tumorigenesis
Representative Cytokines Full List of Cytokines Tested Data-Supported Products
Cytokines, small signaling proteins released by cells, play multifaceted roles in tumorigenesis, acting as a double-edged sword in the tumor microenvironment. On one hand, they can inhibit tumor growth through immune surveillance mechanisms, promoting the differentiation, proliferation, and activity of immune cells such as T cells and natural killer cells, thus facilitating the destruction of tumor cells. On the other hand, cytokines can also promote tumorigenesis by enhancing tumor cell proliferation, survival, and migration. For example, pro-inflammatory cytokines like IL-6 and TNF-α can create a chronic inflammatory environment that supports tumor development and progression, by inducing DNA damage, promoting angiogenesis, and suppressing anti-tumor immune responses. Furthermore, certain cytokines can contribute to the creation of an immunosuppressive tumor microenvironment, enabling tumor cells to evade immune detection and destruction. Additionally, cytokines influence the process of metastasis by modulating the extracellular matrix and enhancing the ability of tumor cells to invade distant tissues. Thus, the complex interplay of cytokines within the tumor microenvironment significantly impacts tumorigenesis, offering potential targets for therapeutic intervention to harness the immune system against cancer.
Figure 1 Structural and Functional Basis of chimeric antigen receptor (CAR).
Representative Cytokines in Tumorigenesis
IL6
Interleukin-6 (IL6) is a multifaceted cytokine that plays critical roles in immune response, inflammation, and hematopoiesis. It is produced by various cell types, including T cells, B cells, macrophages, and fibroblasts, in response to infections and tissue injuries. IL6 operates through binding to its receptor, IL6R, activating intracellular signaling pathways such as the JAK/STAT, MAPK, and PI3K-AKT pathways, which are pivotal for the regulation of immune responses, cell survival, proliferation, and differentiation. In tumorigenesis, IL6 acts as a double-edged sword. On one hand, it can exert anti-tumor activities by enhancing the cytotoxic effects of T cells and natural killer cells. On the other hand, IL6 is implicated in promoting tumorigenesis through several mechanisms. It can foster a tumor-promoting inflammatory environment, stimulate tumor growth and survival, enhance angiogenesis, and facilitate tumor metastasis. Additionally, IL6 contributes to the creation of an immunosuppressive microenvironment that inhibits anti-tumor immune responses, enabling tumor cells to evade immune surveillance.
Recommended Human Anti-IL6 mAb (CAT#: HPAB-S0077-YC)
Figure 2 The purity of HPAB-S0077-YC was greater than 95% as determined by SEC-HPLC.
Recommended Humanized Anti-IL6 mAb (CAT#: TAB-253)
Figure 3 SDS-PAGE analysis of TAB-253 in non-reduced (Lane 1) and reduced (Lane 2) conditions.
Recommended Human Anti-IL6 mAb (CAT#: TAB-097)
Figure 4 ELISA analysis of TAB-097 was performed by coating with human IL6 protein (His tag). Then blocked with BSA and incubated with TAB-097. The HRP-conjugated goat anti-IgG was used as a secondary antibody (1: 2000). Detection was performed using TMB substrate and stopped with sulfuric acid. The absorbances were read on a spectrophotometer at 450 nm.
IFNG
IFNG (interferon gamma, IFN-γ) is a pivotal cytokine primarily produced by T cells and natural killer cells as part of the immune system's response to pathogens and tumors. It plays a complex and dual role in tumorigenesis, functioning as both a promoter and inhibitor depending on the context of the tumor microenvironment. IFN-γ exerts its antitumor effects by inhibiting cell proliferation, inducing apoptosis, and enhancing the antigen presentation capability of immune cells, thereby facilitating the recognition and elimination of tumor cells. It also activates macrophages and promotes the differentiation of T cells into Th1 cells, bolstering the immune response against cancer cells. Conversely, in certain conditions, IFN-γ can contribute to tumor progression by inducing immune checkpoint molecules like PD-L1 on tumor cells, which can suppress the immune response and promote tumor immune evasion. Additionally, chronic exposure to IFN-γ can lead to the selection of tumor cells that are resistant to its antiproliferative effects, thereby contributing to tumor progression. Thus, the role of IFN-γ in cancer is multifaceted, reflecting a delicate balance between its tumor-suppressive functions and its potential to support tumor growth and immune escape under specific microenvironmental conditions.
Recommended Human Anti-IFNG mAb (CAT#: TAB-041)
Figure 5 HPLC analysis of TAB-041 shows the purity is>95%.
Recommended Mouse Anti-IFNG mAb (CAT#: ZG-0146U)
Figure 6 Immunohistochemical of paraffin-embedded human cervical using ZG-0146U at dilution of 1:200.
IL21
Interleukin-21 (IL-21) is a pleiotropic cytokine produced primarily by CD4+ T cells, including Th17, Th9, and follicular helper T (Tfh) cells, playing a crucial role in the regulation of the immune system. Its receptor, IL-21R, is expressed on a variety of hematopoietic cells, such as B cells, T cells, natural killer (NK) cells, and dendritic cells, allowing IL-21 to influence a broad range of immune responses. In the context of tumorigenesis, IL-21 exhibits dual roles, acting both as a promoter and a suppressor. On one hand, it enhances the cytotoxic activity of NK cells and CD8+ T cells, contributing to anti-tumor immunity by promoting the eradication of cancer cells. On the other hand, IL-21 can contribute to tumor progression by supporting the survival, proliferation, and differentiation of certain B cell malignancies, such as in cases of Hodgkin's lymphoma. Furthermore, IL-21's ability to induce the production of pro-inflammatory cytokines can inadvertently support a tumor-promoting microenvironment, facilitating immune evasion and the proliferation of tumor cells.
Recommended Humanized Anti-IL21 mAb (CAT#: TAB-415CL)
Figure 7 Western blot analysis of TAB-415CL was performed by loading human IL21 protein onto a 12% Tris-HCl polyacrylamide gel. Proteins were transferred to a CN membrane and blocked with 5% skim milk for at least one hour. Membranes were probed with TAB-415CL and a HRP goat anti-IgG (H+L) was used as the secondary antibody (1: 3000). Chemiluminescent detection was performed.
Recommended Human Anti-IL21 mAb (CAT#: TAB-577LC)
Figure 8 ELISA analysis of TAB-577LC was performed with Human IL21 Protein. The secondary antibody: HRP-goat-Anti-Human IgG (H+L).
Full List of Cytokines in Tumorigenesis
| Biomarker | Alternative Names | Gene ID | UniProt ID | Roles |
| CXCL8 | C-X-C Motif Chemokine Ligand 8; Monocyte-Derived Neutrophil Chemotactic Factor; Monocyte-Derived Neutrophil-Activating Peptide; Granulocyte Chemotactic Protein 1; Chemokine (C-X-C Motif) Ligand 8; Beta Endothelial Cell-Derived Neutrophil Activating Peptide; Lung Giant Cell Carcinoma-Derived Chemotactic Protein; Lymphocyte Derived Neutrophil Activating Peptide; Alveolar Macrophage Chemotactic Factor I; Tumor Necrosis Factor-Induced Gene 1; Neutrophil-Activating Peptide 1; T-Cell Chemotactic Factor; Interleukin 8; Emoctakin; GCP-1; MDNCF; MONAP | 3576 | P10145 | CXCL8 (C-X-C Motif Chemokine Ligand 8) is a Protein Coding gene. Diseases associated with CXCL8 include Bronchiolitis and Extrinsic Allergic Alveolitis. Among its related pathways are PEDF Induced Signaling and Bacterial infections in CF airways. Gene Ontology (GO) annotations related to this gene include chemokine activity and interleukin-8 receptor binding. An important paralog of this gene is PPBP. |
| IFNG | IFG; IFI; IMD69 | 3458 | P01579 | This gene encodes a soluble cytokine that is a member of the type II interferon class. The encoded protein is secreted by cells of both the innate and adaptive immune systems. The active protein is a homodimer that binds to the interferon gamma receptor which triggers a cellular response to viral and microbial infections. Mutations in this gene are associated with an increased susceptibility to viral, bacterial and parasitic infections and to several autoimmune diseases. |
| IL10 | CSIF; TGIF; GVHDS; IL-10; IL10A | 3586 | P22301 | The protein encoded by this gene is a cytokine produced primarily by monocytes and to a lesser extent by lymphocytes. This cytokine has pleiotropic effects in immunoregulation and inflammation. It down-regulates the expression of Th1 cytokines, MHC class II Ags, and costimulatory molecules on macrophages. It also enhances B cell survival, proliferation, and antibody production. This cytokine can block NF-kappa B activity, and is involved in the regulation of the JAK-STAT signaling pathway. Knockout studies in mice suggested the function of this cytokine as an essential immunoregulator in the intestinal tract. Mutations in this gene are associated with an increased susceptibility to HIV-1 infection and rheumatoid arthritis. |
| IL17 | Interleukin 17A | 3605 | Q16552 | The protein encoded by this gene is a proinflammatory cytokine produced by activated T cells. This cytokine regulates the activities of NF-kappaB and mitogen-activated protein kinases. This cytokine can stimulate the expression of IL6 and cyclooxygenase-2 (PTGS2/COX-2), as well as enhance the production of nitric oxide (NO). High levels of this cytokine are associated with several chronic inflammatory diseases including rheumatoid arthritis, psoriasis and multiple sclerosis. [provided by RefSeq, Jul 2008] |
| IL21 | Interleukin 21 | 59067 | Q9HBE4 | This gene encodes a member of the common-gamma chain family of cytokines with immunoregulatory activity. The encoded protein plays a role in both the innate and adaptive immune responses by inducing the differentiation, proliferation and activity of multiple target cells including macrophages, natural killer cells, B cells and cytotoxic T cells. Dysregulation of this gene plays a role in multiple immune-mediated diseases including lupus, psoriasis and chronic inflammatory diseases. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011] |
| IL6 | Interleukin 6# | 3569 | P05231 | This gene encodes a cytokine that functions in inflammation and the maturation of B cells. In addition, the encoded protein has been shown to be an endogenous pyrogen capable of inducing fever in people with autoimmune diseases or infections. The protein is primarily produced at sites of acute and chronic inflammation, where it is secreted into the serum and induces a transcriptional inflammatory response through interleukin 6 receptor, alpha. The functioning of this gene is implicated in a wide variety of inflammation-associated disease states, including suspectibility to diabetes mellitus and systemic juvenile rheumatoid arthritis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015] |
| IL8 | IL8; Granulocyte Chemotactic Protein 1; MONAP; MDNCF; Beta Endothelial Cell-Derived Neutrophil Activating Peptide; GCP-1; IL-8; Chemokine (C-X-C Motif) Ligand 8; Alveolar Macrophage Chemotactic Factor I; Neutrophil-Activating Protein 1; LYNAP; Monocyte-De | 3576 | P10145 | The protein encoded by this gene is a member of the CXC chemokine family. This chemokine is one of the major mediators of the inflammatory response. This chemokine is secreted by several cell types. It functions as a chemoattractant, and is also a potent angiogenic factor. This gene is believed to play a role in the pathogenesis of bronchiolitis, a common respiratory tract disease caused by viral infection. This gene and other ten members of the CXC chemokine gene family form a chemokine gene cluster in a region mapped to chromosome 4q. |
| Tgfb1 | TGF beta 1; TGFβ1 | 21803 | P28907 | TGFβ1 is a cytokine, whose full name is Transforming Growth Factor Beta 1. It is a protein that regulates cell proliferation, differentiation, and embryonic development, and also plays an important role in immune regulation, inflammatory responses, and tumor development. |
| TNF | DIF; TNFA; TNFSF2; TNLG1F; TNF-alpha | 7124 | P01375 | This gene encodes a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophages. It can bind to, and thus functions through its receptors TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. This cytokine is involved in the regulation of a wide spectrum of biological processes including cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. This cytokine has been implicated in a variety of diseases, including autoimmune diseases, insulin resistance, psoriasis, rheumatoid arthritis ankylosing spondylitis, tuberculosis, autosomal dominant polycystic kidney disease, and cancer. Mutations in this gene affect susceptibility to cerebral malaria, septic shock, and Alzheimer disease. Knockout studies in mice also suggested the neuroprotective function of this cytokine. |
Tested Data-Supported Products for Cytokines in Tumorigenesis
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Reference
- Kartikasari, Apriliana ER, et al. "Tumor-induced inflammatory cytokines and the emerging diagnostic devices for cancer detection and prognosis." Frontiers in Oncology 11 (2021): 692142.
For research use only. Not intended for any clinical use.
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