T Cell Transport and Infiltration

According to the spatial distribution of cytotoxic immune cells in the tumor microenvironment (TME), tumors can be divided into immune inflammation, also known as hot tumors, immune rejection, and immune desert phenotypes. Immune rejection and immune desert tumors are also known as "cold tumors." Hot tumors are characterized by enhanced IFN-γ signaling, high T-cell infiltration, and high tumor mutational burden (TMB). Creative Biolabs offers a range of strategies that target the tumor microenvironment to promote T cell infiltration to heat cold tumors.

Fig.1 The process that drives T cells into the TME.¹

Our Service - Targeting the Tumor Microenvironment

• Methods to facilitate T cell transport and infiltration
  Increases immune checkpoint abundance, promotes efficient tumor infiltration of T cells, and contributes to the warming of cold tumors. Creative Biolabs offers the following treatments that promote T cell transport and infiltration:
  
  • Inhibition of carcinogenic pathways

  Inhibition of oncogenic pathways helps reverse intrinsic T cell rejection. Creative Biolabs provides a series of services and products related to the PI3K-AKT pathway, including but not limited to molecular studies, in vitro and in vivo evaluation of the PI3K-AKT pathway. Studies have shown that treatment of CT26 syngeneic mouse tumors with CDK4/6 inhibitors increases tumor-infiltrating T lymphocytes and significantly upregulates T cell activity.

  • Inhibition of epigenetic modification

  Creative Biolabs provides multiple mechanistic pathways to shift tumors from an immune "cold" state to an immune "hot" state through epigenetic therapy. Some epigenetic-related drugs can enhance the expression of chemokines such as CCL5, CXCL9 and CXCXL10 and promote T cell transfer to tumors. DNMT inhibitors can upregulate the expression of MHC-I in breast tumor cells, enhance IFN-γ response, and promote T cell recruitment to tumors.

  • Anti-angiogenic therapy (AT)

  Persistent angiogenesis due to an imbalance between pro-angiogenic and anti-angiogenic signals is one of the characteristics of tumors. AT can overcome tumor vascular abnormalities, improve tissue perfusion, and increase infiltration of immune effector cells.

• Inhibition of TGFβ/CXCR4

Creative Biolabs evaluated the impact of combination therapy with anti-PD-L1 and anti-TGFβ antibodies on tumor burden by providing corresponding animal models, such as a mouse breast cancer model with an immune rejection phenotype, on tumor-infiltrating T cells, particularly CD8+ T effector cells. We also provide PDAC models to evaluate the effect of CXCR4 inhibitors on T cell accumulation and tumor regression.

We are here to share with you the latest cutting-edge research on tumor microenvironment to help you better understand!

• Published Data

Paper Name:

USP8 inhibition reshapes an inflamed tumor microenvironment that potentiates the immunotherapy

Conclusion:

Inhibition of the deubiquitinating enzyme USP8 remodels the tumor immune microenvironment (TME) and turns "cold tumors" into "hot tumors", thereby enhancing the molecular mechanism of tumor immunotherapy efficacy.

Results:

For more strategies on heating cold tumors, you can visit the Targeting Tumor Microenvironment Services for Cancer Immunotherapy unit! Or you can contact us directly to get the information you need.

References

1. Liu, Yuan-Tong, and Zhi-Jun Sun. "Turning cold tumors into hot tumors by improving T-cell infiltration." Theranostics. (2021) 11,11 5365-5386.
2. Xiong, Wenjun.; et al. "USP8 inhibition reshapes an inflamed tumor microenvironment that potentiates the immunotherapy." Nature communications. (2022) 13,1 1700.

For Research Use Only | Not For Clinical Use