The efficacy of PD-1/PD-L1 blockade in cold cancers and future perspectives

Area of Science:

• Oncology
• Immunology
• Cancer Research

Background:

• Colorectal, breast, ovarian, pancreatic, and prostate cancers are typically low-immune-reactive, characterized by limited immune cell infiltration or presence of immunosuppressive T cells.
• The programmed death ligand 1 (PD-L1) and programmed death-1 (PD-1) interaction is crucial for tumor immune evasion.
• While PD-L1 expression often predicts response to immune checkpoint inhibition (ICI), high PD-L1 levels can also indicate a poor prognosis.

Purpose of the Study:

• To explore the role of PD-L1 expression and tumor-infiltrating lymphocytes (TILs) in predicting immunotherapy response.
• To investigate the efficacy of combining anti-PD-1/PD-L1 therapy with other immunomodulatory agents.

Main Methods:

• Analysis of PD-L1 expression and TIL infiltration in various low-immune-reactive cancers.
• Review of clinical data on responses to anti-PD-1/PD-L1 immunotherapy, particularly in triple-negative breast cancer (TNBC).
• Evaluation of combination therapies involving ICI and agents targeting CXCR4, PARP, or TGF-β.

Main Results:

• Both PD-L1 expression and TIL infiltration appear necessary for enhanced responses to anti-PD-1/PD-L1 immunotherapy.
• Triple-negative breast cancer (TNBC), despite its aggressiveness, shows meaningful responses to ICI.
• Combination therapies have demonstrated significant clinical benefits.

Conclusions:

• Optimizing anti-PD-1/PD-L1 immunotherapy may require strategies that increase both PD-L1 expression and TIL infiltration.
• Combination approaches with immunomodulatory drugs offer promising therapeutic avenues for low-immune-reactive cancers.