From the Research
Role of Checkpoint Blockade Immunotherapy in Prostate Cancer
The role of checkpoint blockade immunotherapy in the treatment of prostate cancer is a complex and evolving field, with various studies investigating its potential benefits and limitations.
- Checkpoint blockade immunotherapy has shown limited efficacy in patients with metastatic prostate cancer, with some studies suggesting that it may be effective in a small subset of patients, such as those with tumors with microsatellite instability 1.
- Combination therapy, such as the use of immune checkpoint inhibitors with other agents like androgen deprivation therapy, may improve clinical response rates to immune checkpoint blockade 2, 3.
- The immunosuppressive tumor microenvironment and acquired resistance are major obstacles to the effectiveness of checkpoint blockade immunotherapy in prostate cancer 4.
- Androgen receptor activity in T cells has been shown to limit checkpoint blockade efficacy, and inhibition of androgen receptor activity in CD8 T cells may enhance responsiveness to PD-1 targeted therapy 5.
Predictors of Response to Immunotherapy
Several factors have been identified as predictors of response to immunotherapy in prostate cancer, including:
- Tumors with microsatellite instability 1
- Tumors with homologous recombination (HR) DNA repair gene mutations, inactivating CDK12 mutations, or underlying mismatch repair deficiency 2
- Prior treatment with bipolar androgen therapy and enzalutamide 2
Future Directions
Future studies are needed to fully understand the mechanisms of primary resistance to checkpoint inhibitors and the tumor immune microenvironment in prostate cancer, and to identify novel combination therapies that can circumvent resistance mechanisms 4, 3, 1.