Immunotherapy has been disappointing as a prostate cancer treatment, but a brand new Columbia study suggests that the powerful treatments have potential when the disease starts to spread.
The study, published in Cancer Cell, found that metastatic prostate tumors contain a wealthy number of immune cells that may potentially be roused by immunotherapy into attacking the cancer.
What we see is that at baseline, lots of the fitting immune cells are already there, but they’re just not attacking the tumors.”
Aleksandar Obradovic, MD, PhD, an associate research scientist on the Vagelos College of Physicians and Surgeons and one in all the lead authors of the study
“That is an exciting finding because prostate cancer has this status for being a ‘cold’ tumor, altogether hidden from the immune system. Our study suggests that, in metastases, this is not at all times the case. And that combining hormone therapy with immunotherapy further stimulates the anti-tumor immune cells, with potential for further optimization and improvement in patient outcomes.”
Reading the tumor microenvironment
Before the Columbia study, nobody had looked deeply into the microenvironment of untreated metastatic prostate cancers, deterred partially by the problem of obtaining samples suitable for single-cell RNA sequencing, particularly before treatment was initiated.
In a clinical trial of men with metastatic prostate cancer, the Columbia researchers also found that hormone therapy combined with immunotherapy triggered an influx of much more immune cells into the tumor’s microenvironment. To handle this data gap, the Columbia researchers designed a clinical trial for a small variety of men to acquire such samples before and after treatment with standard chemo-hormonal therapy and immunotherapy.
“One goal of this study was to deeply profile what the microenvironment looks like after which see what happened when the tumors were treated with the mix of chemo-hormonal therapy and immune therapies,” Obradovic says.
These analyses were also made possible with recent cutting-edge bioinformatics tools, previously developed by the Columbia researchers, that were in a position to reveal many forms of cells within the tumor microenvironment not distinguishable by standard techniques.
Immune cell signatures suggest possible treatments
Along with finding a various community of immune cells inside metastatic tumors, various from organ to organ, the researchers discovered that some subgroups of immune cells predicted worse response to treatment.
A few of the patients’ tumors, for instance, were full of T cells that produce TNF-alpha, which has been related to suppression of the anti-tumor immune response. “We see that patients with loads of those cells had worse outcomes,” Obradovic says, “and it’s possible we could potentially improve outcomes in these patients by adding FDA-approved TNF alpha inhibitors to their regimen.”
The researchers are planning additional trials to check these ideas and are continuing to investigate samples from patients spanning the range from primary through late metastatic prostate cancer to realize a more complete understanding of the evolution of those tumors’ microenvironment.
Hawley, J. E., et al. (2023). Anti-PD-1 immunotherapy with androgen deprivation therapy induces robust immune infiltration in metastatic castration-sensitive prostate cancer. Cancer Cell, 41(11), 1972-1988.e5. doi.org/10.1016/j.ccell.2023.10.006.