Despite previous disappointments in using immunotherapy for prostate cancer treatment, a recent study from Columbia University indicates promising potential for these powerful treatments, especially as the disease progresses.
Published in Cancer Cell, the study reveals that metastatic prostate tumors harbor a diverse array of immune cells that could be activated by immunotherapy to target and combat the cancer.
Dr. Aleksandar Obradovic, one of the lead authors and an associate research scientist at the Vagelos College of Physicians and Surgeons, explains, “Our findings show that many of the right immune cells are already present in metastatic prostate tumors, but they are not effectively attacking the tumors initially. This discovery is significant because prostate cancer is often considered a ‘cold' tumor, seemingly invisible to the immune system. Our study challenges this perception, suggesting that in metastases, this may not always be the case. Moreover, combining hormone therapy with immunotherapy appears to further activate anti-tumor immune cells, presenting opportunities for optimization and potential improvements in patient outcomes.”
Reading the tumor microenvironment
Exploring the microenvironment of untreated metastatic prostate cancers had been largely uncharted territory before the Columbia study, primarily due to the challenges associated with obtaining suitable samples for single-cell RNA sequencing, especially pre-treatment initiation.
In a clinical trial involving men with metastatic prostate cancer, the Columbia researchers observed that the combination of hormone therapy and immunotherapy led to a significant increase in immune cell presence within the tumor's microenvironment. To bridge the gap in understanding, the researchers devised a clinical trial involving a small group of men to obtain samples both before and after treatment with the standard chemo-hormonal therapy and immunotherapy.
Dr. Aleksandar Obradovic explains, “Our study aimed to comprehensively profile the microenvironment and investigate the impact of treating tumors with the combination of chemo-hormonal therapy and immune therapies.”
These analyses were facilitated by state-of-the-art bioinformatics tools developed by the Columbia researchers, allowing the identification of various cell types within the tumor microenvironment that were previously indistinguishable using conventional techniques.
Immune cell signatures suggest possible treatments
Beyond uncovering a diverse array of immune cells within metastatic tumors, with variations observed between organs, the researchers identified certain subgroups of immune cells that predicted a less favorable response to treatment.
In some patients' tumors, an abundance of T cells producing TNF-alpha, linked to the suppression of the anti-tumor immune response, was evident. Dr. Aleksandar Obradovic notes, “Patients with a high presence of these cells experienced worse outcomes. Introducing FDA-approved TNF alpha inhibitors to their treatment regimen could potentially enhance outcomes in these cases.”
The researchers are now planning additional trials to validate these findings and are persistently analyzing samples across the spectrum from primary to late metastatic prostate cancer. This ongoing work aims to provide a more comprehensive understanding of the microenvironment evolution in these tumors.