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Updated: Oct 28, 2025
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Targeting the spectrum of immune checkpoints in prostate cancer
Laura A Sena1, Samuel R Denmeade1,2, Emmanuel S Antonarakis1,2,3
1Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Abstract:
Introduction: The proven efficacy of the cellular vaccine sipuleucel-T in 2010 led to optimism about immunotherapeutic approaches for the treatment of prostate cancer. Some surmised that prostate cancer might be an ideal target for immune-mediated killing given that the prostate is not an essential organ and expresses unique proteins including prostate-specific antigen, prostate-specific membrane antigen, and prostatic acid phosphatase that could be targeted without side effects. Subsequently, antibodies that inhibit the T cell checkpoints PD1 and CTLA4 were shown to stimulate antitumor immune responses, leading to tumor regression in several cancer types. These therapies have since been tested in several studies as treatments for prostate cancer, but appear to have limited efficacy in molecularly unselected patients.Areas covered: In this review, we discuss these studies and evaluate features of prostate cancer and its host environment that may render it generally resistant to CTLA4 and PD1 blockade. We provide an overview of alternate immune checkpoints that may hold greater significance in this disease.Expert opinion: Combination therapies to target multiple layers of alternate immune checkpoints may be required for an effective immune response to prostate cancer. We discuss combination therapies currently being investigated.
Insights
Prostate cancer shows limited response to current immune checkpoint inhibitors like PD1 and CTLA4. Combination therapies targeting alternate immune checkpoints are likely needed for effective prostate cancer immunotherapy.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Sipuleucel-T's efficacy spurred interest in immunotherapy for prostate cancer.
- Prostate cancer's unique antigens and non-essential organ status suggested immune targeting potential.
- PD1 and CTLA4 inhibitors have shown success in other cancers but limited efficacy in prostate cancer.
Purpose of the Study:
- To review studies on PD1 and CTLA4 blockade in prostate cancer.
- To evaluate prostate cancer's resistance mechanisms to current immunotherapies.
- To identify alternative immune checkpoints relevant to prostate cancer.
Main Methods:
- Literature review of clinical studies on immune checkpoint inhibitors in prostate cancer.
- Analysis of prostate cancer's tumor microenvironment and molecular characteristics.
- Exploration of alternative immune checkpoint pathways.
Main Results:
- Prostate cancer exhibits resistance to PD1 and CTLA4 blockade in unselected patients.
- Specific features of prostate cancer and its host environment contribute to immunotherapy resistance.
- Alternative immune checkpoints may play a more critical role in prostate cancer immunity.
Conclusions:
- Current immune checkpoint inhibitors have limited efficacy in unselected prostate cancer patients.
- Combination therapies targeting multiple immune checkpoints are necessary for effective prostate cancer treatment.
- Further research into alternative immune checkpoints and combination strategies is warranted.
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