Tumor Microenvironment: T Cell Exclusion

An immunosuppressive tumor microenvironment (TME) is able to preferentially restrict accumulation of T cells in the vicinity of cancer cells. Several mechanisms by which the TME can exclude T cells have been described and are outlined below, but a better understanding of these mechanisms is needed. The potential clinical efficacy of therapeutic strategies that target T cell exclusion mechanisms also needs to be assessed. Click the links to browse our offering of relevant proteins, antibodies, ELISAs, kits, and small molecules.

Tumor Microenvironment Homepage


Cancer-associated Fibroblasts (CAFs)

CAFs, which can be identified by expression of the membrane protein Fibroblast Activation Protein alpha/FAP, suppress anti-tumor immune responses by restricting T cells to the stroma and preventing them from accumulating in the vicinity of cancer cells by at least two mechanisms.

  • Production of dense extracellular matrix (ECM)
    • Immunosuppression – the dense ECM traps T cells in the stroma, denying them access to cancer cells.
    • Potential therapeutic strategy - Both collagenase and CCL5 have been shown to increase T cell movement out of stromal regions and into the vicinity of cancer cells.
  • Secretion of CXCL12
    • Immunosuppression – CAF-secreted CXCL12 coats T cells and excludes them in a CXCR4-dependent manner.
    • Potential therapeutic strategyCXCR4 inhibitors increase T cell numbers in the vicinity of cancer cells and improve efficacy of anti-PD-L1 antibody treatment.


Identify FAP+ CAFs
IHC data - FAP antibody
Detection of FAP in Human Basal Cell Carcinoma by IHC
  Trust R&D Systems® Cytokines
Data - CCL5-mediated chemoattraction
CCL5-mediated Chemoattraction


Reactive Nitrogen Species

Graphic of adoptive cell transfer
Find Products for Adoptive Cell Transfer Research

Reactive nitrogen species can induce the nitration of proteins. This post-translational modification has a wide range of functional consequences depending on the protein modified. The production of reactive nitrogen species by myeloid-derived suppressor cells (MDSCs) within the TME leads to T cell exclusion.

  • Nitration of CCL2
    • ImmunosuppressionCCL2 nitration results in the trapping of T cells in the stroma surrounding tumor cells.
    • Potential therapeutic strategy – Inhibition of CCL2 nitration has been shown to enhance the accumulation of tumor-infiltrating lymphocytes (TILs) and improve efficacy of adoptive T cell therapy.



Tumor Vasculature

The tumor vasculature is involved in the preferential recruitment of other immune cells in place of effector T cells to the tumor microenvironment. Multiple mechanisms by which the tumor vasculature can override the effects of chemotactic signals for T cell extravasation and recruitment to the tumor have been described.


MagCellect Cell Isolation Kits

Data - Isolation if CD8 T Cells

Isolation of CD8+ T Cells using the MagCellect Cell Isolation Kit


  • VEGF and B7-H3 or EDNRB/Endothelin R Type B
    • Immunosuppression – Decreased T cell infiltration and worse clinical outcome have been correlated with elevated VEGF levels along with expression of either B7-H3 or EDNRB/ETBR on tumor vessels.
    • Potential therapeutic strategy – Treatment with EDNRB/ETBR inhibitors inhibitors inhibitors increased T cell adhesion to endothelial cells, which resulted in elevated TILs and an anti-tumor response to an otherwise ineffective anticancer vaccine. Inhibitors of VEGF and VEGF R2 also increase TILs and improve immunotherapy efficacy. TNF-alpha treatment has been reported to normalize blood vessels and increase CD8+ T cell infiltration and efficacy of ACT.


Block B7-H3 Function
Data - bioassay for a B7-H3 neutralizing antibody
Neutralization of B7-H3-induced Proliferation using a B7-H3 Antibody
  Inhibit VEGF R2 Signaling
Structure if VEGF R inhibitor, Axitinib
Axitinib: Potent VEGF R1, -2, and -3 Inhibitor