Immunotherapy Fails When Your Immune Cells Can’t Reach the Tumor | Dr. Dino Prato

Dr. Prato explores a critical reason why immunotherapy for cancer often falls short: T-cells and other immune cells can't reach the cancer cells.

He details a phenomenon where crucial t lymphocytes are blocked from entering tumors, preventing them from doing their job. Understanding this challenge in immunology is key to advancing effective cancer treatment strategies.

🎯 What You’ll Learn in This Episode

• What T-cell exclusion means
• Why immune cells may be blocked from tumors
• What “cold tumors” really are
• How tumor microenvironment affects treatment response
• The role of CXCR4 and CXCL12 signaling
• Why immunotherapy doesn’t work for every patient
• How immune positioning impacts outcomes
• Why personalized approaches are being explored

📍 Envita Medical Centers – Scottsdale, AZ
🌐 Learn more: www.envita.com
📞 Speak with a care coordinator: 866-830-4576

“Sometimes the immune system isn’t weak — it’s locked out.”

Disclaimer
This podcast is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always consult your licensed healthcare provider before making any medical decisions. Individual results will vary, and Envita Medical Centers does not guarantee outcomes. Some treatments discussed may not be FDA-approved or available in all locations. Testimonials are shared with patient consent and may not reflect typical results. Do not delay or disregard professional medical care based on the podcast's content. Certain treatments may be available only at Envita’s international clinic in Hermosillo, Mexico. No specific outcomes are promised or implied.
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Outcomes Disclaimer
The results referenced from Envita's Precision Cancer Care: 35-Fold Improvement in Response Rates are from a retrospective analysis of 199 late-stage cancer patients treated at Envita Medical Centers between 2021 and 2023, as published in the Journal of Cancer Therapy. These outcomes are not guaranteed and will vary based on individual factors such as cancer type, stage, genetics, immunity and prior treatments. Any comparisons to standard care or clinical trials are based on published data and internal analysis, not head-to-head studies. Individual results will vary.

You can read the full peer-reviewed study at: 

https://www.scirp.org/journal/paperinformation?paperid=132493

Transcript

SPEAKER_00 0:08

Your immune system just found the cancer, but there's a wall. And the cells could save your life if they could just get in there and kill the cancer, but they're locked outside. And this is why immunotherapy fails for so many patients. Not just because your immune system was weak, not just because the drug wasn't the right selection, but because your T cells and your natural killer cells can't reach the tumor. They're standing at the door and nobody gave them the key. A new study published in gastroenterology highlights a major reason why this happens. It's called T cell exclusion. The immune cells are present, but they can't enter the tumor. And it points to an FDA-approved drug called plearexophore. Originally used for transplant patients to mobilize stem cells. It has an off-label usage here in which we use with patients a different purpose to help with turning cold tumors hot. But huge immune implications with this drug. Plorexaphore blocks a pathway that can act like a keep it out signal for your immune system. And when researchers disrupted this signal in the human tumor work, the immune cells move towards the tumor core and the tumor cells died. And then they did better. They had a better chance to respond and engage because the key is immunity. Remember, the first and last offense against cancer is your immune system. This isn't theory. This is the key. Now, oftentimes you're waiting for a brand new drug to come to market as a specialty. When we use this directed tumor, we can see cold tumors become hot. But here's what the study didn't tell anyone. Delivering it through IV is not really the best way to do it. The best way to deliver it in our clinical experience is directed tumor. Now, there's many drugs that we custom build for patients based on their deep mapping that allows us to go deep to tumor. So I want to share this with you. When you're looking at the tumor microenvironment, everybody's gonna be a little bit different. So today I'm just talking about one drug, pleorexophore. But late-stage tumors have different ways of becoming resistant. They can develop what we call cancer-associated fibroblasts, these cells hijacked by the tumor to overproduce dense structural proteins, primary collagen, hyaluronin, these stromal barriers, and the result, a dense scar tissue or a desmoplasia around the tumor that creates a problem. So it creates a place where these T cells get trapped and they crawl and they're trying to get through cement to try to get to the tumor. And we can overcome that. And we see this in breast, prostate, lung, pancreatic colon, you name it. All kinds of advanced cancers can have these intense barriers. In this episode, I will show you how to overcome this. This is huge. This is a common thing in late-stage cancers, how to overcome it, both with technique, plexophore, and other drugs that can be custom built for the patient. I'm Dr. Dino Prado, founder of NVITA Medical Center. For the last 25 years, my team and I have helped thousands of patients, including many that have failed some of the top cancer hospitals across the country. And we did it with precision targeting and techniques like SIPI, which I'm going to go into today, and techniques that have helped us turn cold tumors hot. Make sure you're working with a doctor before you change anything. Let's get started. Let me break this down so it makes sense. Most people think cold tumors mean the immune system isn't responding. But that's not always true. Many times the immune system can be, yes, have exhaustion, but there's different methods of evasion. It's not responding. The immune system can't get to the tumor, meaning the T cells are in the wrong place. This study looked at liver cancer, carcinomas, and they found something shocking. The T cells were present, but they were stuck. They were trapped in this fibrous tissue outside of the tumor and they couldn't get to killing the cancer cells. So they were like trying to call 911 to get in, the fire trucks, everything, but nothing would come to get in there. The gates were closed. And this is why patients lose time, because they may have a very dense stromal barrier and tissue blocking their immune system from getting to the cancer. Because the architecture of the tumor won't let it work. And this is where, even if you're doing chemotherapy or IV chemotherapy, 98 to 99% of the drug is not making it. You might get 1% actually making it to the tumor or less than that. Now, here's where it gets a little technical, but stay with me because this is the key to everything. Inside many solid tumors, especially the ones that don't respond well to immunotherapy, there's a molecular shield and it's called CXCR4 or CXCL12. Here's how it works CXCL12 is a chemical signal released by the tumor. It's a sign that says keep out. And CXCR4 is a receptor on your T cells that reads the sign and says, I can't go in right now. So the tumor literally repels your own immune system. Isn't that crazy? That's how powerful tumor evasion can be. And here's the worst part this shield can be the strongest in tumors that need the most immune help, meaning they're cold, or they're called microsatellite stable cancers, MSS, meaning they're cold. These include many colorectal, breast, pancreatic, prostate, gastric, ovarian, and many others where checkpoint inhibitors don't work. They're not indicated. But if they are, they only work for a portion of the patients. I've said this before, like in Frontiers and Oncology, has reported that people that use PD1 inhibitors, only 10% have a long-term response. But people that have MSS don't even get these. They don't have any immunotherapy on board because these tumors may be too cold. And so here's how we change that. So you're not stuck by using no immunotherapy because you need immunotherapy to really get the responses that you want. So if you've been told immunotherapy won't work for you for your cancer type, sometimes this is the biology behind the statement, is what I'm going over with you today. Plexophore was originally approved to help move stem cells out of the bone marrow for transplant-related uses. But researchers discovered something incredible. It blocks CXCR4, which means it can shut down the tumor's keep out signal. And when they tested it, T cells started moving into the tumor core and killing it. Not around it, not near it, but inside, exactly where you want your immune system to go. But here's where it gets even more important. In the study, it tested systemically, meaning through IV care. That's not the only way this works. It actually works better when delivered directly to the tumor using invisible surgery. In our clinical experience, when you use interventional radiology oncology and go into the tumor with a catheter as small as your hair follicle, into the blood vessels, right to the tumor, and deliver it and come out. And you're done with a band-aid, why we call it invisible surgery or minimally invasive, we can get the medicines right to where we need to. And here's why that matters. When you give plexophore systemically, you're sending the signal to the whole body, not right where you want it. You can't concentrate it around the actual stromal areas. But when you target the tumor directly, you're doing something to the tumor that goes way beyond just opening up the T cells. You're fracking the tumor like you're fracking oil. You're opening up all the neoantigens, all the damage-associated molecular patterns, all the tumor fragments to the immune system at the same time opening it up to the stromal barrier. This is very powerful. So you're giving all the new neoantigens to your immune systems, your dendritic cells that are the detectives. They grab all this stuff like the fingerprints and the mugshots and they pass it to your T cells, and now they can penetrate. This treatment becomes even more powerful for patients. And we don't just use one tool, we use combinations in rebuilding the immune system at the localized tumor so that the rest of the body can recognize the cancer cells and get rid of them using the body's immune system. This is precision oncology. It's absolutely brilliant and minimally invasive. So this is why chemoimmunoprecision injections that we use using interventional radiology oncology makes a big difference in precision oncology. So here's what happens: Step one, deep testing to see if a patient's a candidate to this or any other combinations they might need. So local treatment now can hit the tumor and trigger an immunogenic cell death. Cancer cells die, and now it alerts the rest of the immune system. In this process, plexophore or other drugs that we can use off-label, this is just one of them, can break the barrier down and let the T cells in if the marker's there for that. Now we can support the T cells through the body's health, immunity, nutrition, lifestyle, phytotherapeutics, get rid of the root causes that may have suppressed the immune system in other areas, and now has almost built its own vaccine against the cancer right at the tumor, teaching your immune system to recognize the cancer throughout your body. This is not just a PD1 therapy, hope and pray. This is precision oncology. We're not just releasing the brakes on the immune system, we're opening the gates to the tumor. So who needs this? It depends. Everybody's gonna be different. Depends on your markers. It depends on the testing, which of the markers you need. Well, we test, we don't just look at a biopsy, tumor marker, and imaging, which is like 24 markers that all the major hospitals use and then put you in a national comprehensive cancer network guideline, basically a protocol for your type of stage of cancer. We're looking at a thousand plus markers, immune profiling, immune spatial biology. And in this data, we're looking at, okay, is the patient MSS? Microsatellite stable? Are there tumors cold? What's blocking it? What's a tumor microenvironment? And then we've custom build the immunotherapy. And if you've been told you're not a candidate for immunotherapy, your tumor is cold, you don't have any treatments, this won't work for you. This is what you need to understand. Many cold tumors aren't truly cold, they're just excluded. The immune system can respond if opened up and given the correct information. And when you use these types of technologies, you get to underlining cause at the tumor level and you're able to now develop custom immunotherapy and deliver it straight to the patient to help them finally respond to treatment in a very powerful way and then train the rest of the immune system to do the same in the body. So if your oncologist says immunotherapy won't work for you, ask them this. Have you evaluated my immune system? Have you done immune profiling, immune spatial biology? Do we know if my T cells are trapped in a stromal barrier? Have you looked at CXCR4 or CXCL12 or other signals and markers? Have you looked at microsatellite stability and how to overcome that? These are the questions you want because if you don't get answers to these questions, you don't get the results and our clinical experience that a patient really wants. So here's how we help patients. We integrate these things with deep planning, targeting, and custom delivery for each patient. That's precision oncology. Now you've opened up your tools. So you've disrupted the tumor architecture, you've released the antigens, you remove the barriers of the immune system, and now your immune system is being trained to fight your cancer. Not some clinical trial, one size fits all drug that was selected for my protocol for you, but exactly what you need. And once your immune system recognizes a tumor, it is a big game changer. We can now optimize metabolic function, inflammatory function, microbiome, and other things to keep the immune system strong. Now, I hope you found this episode helpful. Share it with somebody who may need it. And more importantly, subscribe so you can help us get the word out there of precision oncology so people don't have to be stuck in the one size fits all. I hope you found this helpful and may the Lord bless you on your journey to healing.