Tumor Microenvironment
Immuno-Oncology
In cancer, both the innate and adaptive arms of the immune system can launch antitumor immune responses to limit cancer growth and progression. However, tumor cells are able to inhibit these responses and enable immune evasion in a variety of ways.
VIEW ALL CANCER IMMUNOLOGY PRODUCTSImmuno-Oncology Screening Library
- Contains >90 compounds
- Includes a variety of immuno-oncology target modulators
STING Signaling
Detection of dsDNA in the cytosol of tumor cells by the nucleic acid sensor cyclic GMP-AMP synthase (cGAS) leads to production and secretion of the cyclic dinucleotide second messenger 2’3’-cGAMP. Uptake of this immunostimulatory second messenger by healthy host cells in the tumor microenvironment (TME) leads to activation of stimulator of interferon genes (STING) and production of type I IFNs and tumor-suppressive immune responses.
- cGAS Inhibitors
- cGAS Inhibitor Screening Assay Kit
- cGAS TR-FRET Inhibitor Screening Assay Kit
- 2'3’-cGAMP (sodium salt)
- 2’3’-cGAMP ELISA Kit
- STING Agonists
- STING Antagonists
STING Signaling Pathway
Explore our tools to study STING signaling, including cyclic dinucleotides, assay kits, inhibitors, proteins, and antibodies.
Download The BrochureAdenosine Signaling
While certain second messengers like 2’3’-cGAMP induce pro-inflammatory responses, other soluble factors in the TME, including adenosine, can suppress antitumor immune responses instead. Extracellular adenosine generated by ecto-5’-nucleotidase (NT5E; CD73) signals through A2A and A2B adenosine receptors to decrease the effector function of cytotoxic CD8+ T cells and induce tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) to produce the anti-inflammatory cytokine IL-10, thereby promoting immunosuppression. Cancer cells can modulate both immunostimulatory 2’3’-cGAMP signaling and immunosuppressive adenosine signaling in the TME via the action of the transmembrane protein ENPP1.
Learn how ENPP1 suppresses immune responses in the TME by inhibiting paracrine STING signaling and promoting adenosine production
Read The ArticleTumor Antigenicity & the PD-1/PD-L1 Checkpoint
Effector T cells can recognize tumor-specific antigens presented by major histocompatibility complex (MHC) molecules on the surface of cancer cells. Cancer cells can reduce their antigenicity and immune detection by downregulating MHC-I. Another strategy employed by cancer cells to avoid destruction by T cells is to express PD-L1 on the cell surface. Following T cell recognition of antigen-bound MHCs on the surface of the cancer cell, PD-L1 can engage the checkpoint receptor PD-1 on the T cell surface, inducing tolerance and preventing destruction of the cancer cell. Several checkpoint inhibitors that interfere with this interaction are currently used in cancer therapy.
Learn more about antigen presentation by MHC molecules and how Cayman's Immunopeptidome Profiling Services analyze MHC-associated peptides to identify tumor neoantigens and potential immunogenic sequences.
WATCH THE VIDEOAngiogenesis
As tumors grow, they require vasculature formation via angiogenesis to supply their cells with oxygen and nutrients and allow for removal of waste products. Under hypoxic conditions, hypoxia-inducible factor-1α (HIF-1α) triggers expression of key mediators of angiogenesis, including vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). Additional proangiogenic factors include FGFs, TGF-β, and angiopoietins.
Invasion & Metastasis
Metastasis is the process by which cancer cells migrate to and establish tumors in secondary sites. To initiate metastasis, tumor cells must first dissociate from the primary tumor and invade the surrounding tissue. This process involves degradation of extracellular matrix (ECM) proteins by matrix metalloproteinases (MMPs), which are upregulated in many cancer types. Subsequent intravasation into nearby blood or lymphatic vessels then allows for transport of the circulating tumor cells to distant sites where they can exit the blood vessel via extravasation and colonize a secondary location.
Tumor cells undergo various biochemical and morphological changes conferred by the epithelial-to-mesenchymal transition (EMT) that increase their motility and invasiveness and allow for remodeling of the ECM, promoting progression through the invasion-metastasis cascade. EMT is characterized by loss of epithelial markers, such as cytokeratins and the cell-cell adhesion molecule E-cadherin, and upregulation of mesenchymal markers, including N-cadherin, vimentin, and fibronectin.
- MMP Inhibitors
- Cytokeratin Antibodies
- E-Cadherin Rabbit Monoclonal Antibody
- N-Cadherin Monoclonal Antibody
- Vimentin Antibodies