Anmbreen Jamroze, Research Assistant Professor at Roswell Park Comprehensive Cancer Center, shared on LinkedIn:
“What If We’ve Been Giving Immunotherapy at the Wrong Time in Prostate Cancer?
A story of scientific curiosity, and a potential new window of opportunity.
Cancer research often begins with a question. Sometimes, the most interesting discoveries emerge when we start questioning something we have long accepted.
For years, prostate cancer has been considered an immunologically ‘cold‘ tumor. Unlike melanoma or lung cancer, where immune checkpoint inhibitors have transformed treatment, prostate cancer has remained remarkably resistant to these therapies.
But something has always intrigued me.
What if the problem isn’t simply that prostate cancer doesn’t respond to immunotherapy? What if we haven’t found the right moment to give it?
That question became central to our recently published research in the Journal for ImmunoTherapy of Cancer (JITC)
When cancer treatment changes the immune landscape
Androgen deprivation therapy (ADT) has been a cornerstone of prostate cancer treatment for decades. Its primary purpose is to suppress the androgen signaling that fuels tumor growth.
But tumors don’t exist in isolation. They live within complex ecosystems of immune cells, stromal cells, and molecular signals.
We wanted to understand how the duration of ADT influences this ecosystem and shapes its evolution over time.
Using prostate tumor specimens from 43 patients treated with neoadjuvant ADT, we did RNA sequencing as well as quantitative multispectral immunofluorescence to examine not just which immune cells were present, but where they were positioned and how the immune landscape differed with treatment duration.
What emerged was a fascinating biological story.
The immune system shows up. But it doesn’t stay the same.
After approximately 3–5 months of ADT, we observed a striking influx of cytotoxic T cells and helper T cells into prostate tumors.
These are precisely the immune populations we hope to engage when treating cancer with immunotherapy.
Even more interestingly, these T cells were clustering near tumor cells, as adaptive immune-response.
For a disease historically described as immunologically cold, this was an encouraging observation.
But the story had an unexpected second chapter.
In tumors exposed to ADT for six months or longer, the immune landscape looked dramatically different.
Cytotoxic T cells declined, while immunosuppressive populations, including M2-like macrophages and regulatory T cells, became more prominent.
The environment that had appeared increasingly immune-active was shifting toward immune suppression.
Same treatment. Different durations. A changing immune landscape.
Could timing be the missing piece?
This is where our findings become particularly exciting.
Perhaps ADT does more than suppress prostate cancer growth. It may also create a temporary opportunity to make tumors more receptive to immune-based therapies.
If checkpoint inhibitors are introduced during this immune-active phase, could we improve their chances of success?
We don’t yet know. Our study was observational and did not test checkpoint inhibitor efficacy.
But it offers a compelling biological rationale for something that deserves greater attention in clinical research: the sequence and timing of therapies may be just as important as the therapies themselves.
Rather than assuming that prostate cancer is permanently immune-resistant, we may need to understand when its immune environment becomes most vulnerable to therapeutic intervention.
Why this discovery matters to me.
As a translational cancer researcher, what motivates me most is connecting what we observe in patient tumors with questions that could ultimately change clinical practice.
A discovery becomes especially meaningful when it challenges how we think about treating a disease.
Our findings do not yet provide a new treatment. They provide something that often comes first: a new way of asking the question.
- Could we use an existing standard-of-care treatment to create a better biological setting for immunotherapy?
- Could we identify that opportunity before immune suppression takes hold?
- And could understanding the dynamic relationship between cancer therapy and the immune system help us design smarter clinical trials?
These are the questions I hope our work will help move forward.
My biggest takeaway is simple: in cancer immunotherapy, knowing what to target matters. But knowing when to target it may be equally important.
And sometimes, the next breakthrough may come not from discovering an entirely new drug, but from learning how to use the treatments we already have more intelligently.
I am deeply grateful to Dr. Kent Nastiuk, Renyuan Zhang and all coauthors for their collective efforts that made this study possible.”
Title: Temporal dynamics of the immune response to neoadjuvant androgen deprivation therapy suggest a window of opportunity for checkpoint inhibitor therapy in prostate cancer
Authors: Anmbreen Jamroze, Renyuan Zhang, Emily Dougherty, Kriti Ahuja, Lei Deng, Karan Jatwani, Uyen V Nguyen, Bailey Farmer, Gaybrielle James, Michalis Mastri, Kevin H Eng, Bo Xu, Yvonne Saenger, Yuanquan Yang, John J Krolewski, Dean G Tang, Gurkamal Chatta, Kent L Nastiuk
Read the Full Article on Journal for ImmunoTherapy of Cancer.
You can also read: FDA Approved Talazoparib Plus Enzalutamide for HRR-Mutated Metastatic Castration-Sensitive Prostate Cancer
