CD155 loss enhances tumor suppression via combined host and tumor-intrinsic mechanisms

Area of Science:

• Immunology
• Oncology
• Molecular Biology

Background:

• Immune suppression beyond PD-1/PD-L1 pathways needs further investigation.
• Nectins and nectin-like molecules are implicated in cell proliferation, migration, and immunomodulation.
• CD155, a nectin-like molecule, is a potential target for cancer immunotherapy.

Purpose of the Study:

• To investigate the role of CD155 in tumor growth, metastasis, and anti-tumor immunity.
• To evaluate the therapeutic potential of targeting CD155 in combination with existing immunotherapies.

Main Methods:

• Analysis of CD155 expression in human and mouse tumors and tumor-infiltrating myeloid cells.
• Assessment of tumor growth and metastasis in CD155 knockout (Cd155-/-) mice.
• Evaluation of immune cell function (CD8+ T cells, NK cells) and DNAM-1 expression.
• Comparison of immunotherapy efficacy (PD-1, CTLA4 blockade) in the presence or absence of CD155.

Main Results:

• CD155 is expressed on malignant and myeloid cells in tumors.
• Cd155-/- mice exhibited reduced tumor growth and metastasis.
• CD155 deletion led to DNAM-1 upregulation and enhanced CD8+ T and NK cell effector functions.
• Tumor-intrinsic CD155 also contributed to slower tumor growth and reduced metastasis.
• Combined CD155 absence on host and tumor cells showed greater inhibition of tumor progression.
• PD-1 or PD-1/CTLA4 blockade was more effective when CD155 was limited.

Conclusions:

• CD155 plays a significant role in promoting tumor growth and metastasis.
• Targeting CD155 enhances anti-tumor immunity by upregulating DNAM-1 and improving T and NK cell function.
• CD155 represents a promising therapeutic target, potentially for combination therapy with PD-1/PD-L1 inhibitors in cancer treatment.