Sperling Prostate Center

Can Focal Laser Ablation Cause a Broad Anti-tumor Immune Effect?

Wouldn’t it be great if a patient with metastatic cancer could simply have the primary tumor treated—then all the others would miraculously start to disappear?

Well, we don’t yet have the such clinical wizardry, but it looks the body itself has such a capacity! It’s called the abscopal effect (pronounced ab-SCOPE-ul). Studies are now revealing that under certain conditions, tumor ablation triggers it. Can it happen with Focal Laser Ablation (FLA)?

The abscopal effect

Evidence suggests it can. It starts in the early 1950s. During animal experiments using radiation to treat primary tumors that had spawned metastatic tumors in multiple locations, it appeared that some of the distant tumors were spontaneously shrinking, even vanishing, after the primary tumor had been radiated. No one had a way to account for this, but they named it abscopal from “the Latin ab meaning ‘position away from’ and scopos ‘a target for shooting at’.”[i] Think of it like being attacked by 5 ninjas but you only have time to shoot one; you kill the first one but to your surprise, the other 4 also drop dead.

Unlike ablation using extreme temperatures, radiation does not immediately kill cancer cells. Instead, it destroys tumors by degrading the DNA in the cancer cells, which are more vulnerable to radiation than healthy cells. The result is gradual; it can take many months for tumors to die off as cancer cells become unable to reproduce themselves due to the DNA damage. Yet something was happening as the cells died off that mediated metastatic tumor cell death beyond the radiated target.

A similar effect was seen in the 1960s when another type of tumor destruction called cryoablation, or freezing, was being tested as a prostate cancer (PCa) treatment. Three cases of the abscopal effect on remote tumors were reported in 1969 following freezing of the primary tumor in patients with metastatic PCa.[ii] This led to a hypothesis that the physical mechanisms of cell destruction due to extreme freezing results in the release of cell surface proteins (antigens) into the bloodstream.

Antigens are specific to the type of cell from which they originate. Thus, they act as “badges” that are “read” and remembered by the immune system. The theory behind this cryoimmunological response was that post-cryo antigens “warn” the immune system of a potential hostile takeover by cancer. Killer T cells then launch an informed seek-and-destroy mission, searching for culprits wearing the identical badge. When they find the same tumor cell lines in other locations (i.e., metastasis) they kill them.

Can FLA trigger an immunological abscopal effect?

The historic evidence suggested that either radiation (no heat) or cryo (extreme freeze) preserved some form of cellular matter that was able to disperse and stimulate a selective immune response against metastasis. It was thought that the high temperatures from heat-based ablations (HIFU, Focal Laser, Radiofrequency) would fail to preserve biochemical “badges” because it denatures cellular matter.

However, a new line of thinking suggests that Focal Laser Therapy (FLA) can be modulated to maximize the possibility of an abscopal effect. Rather than a brief (about 2 minutes) burst of intense heat that causes immediate cell death for all cells encompassed by the globe of laser light, a lower temperature for a prolonged duration would kill cancer cells more slowly. In the death process, their biochemical “badges” would disperse into the bloodstream, since they hadn’t been denatured by blazing heat.

This thinking was based on physics. Where the tip of the laser fiber emits the laser light into surrounding tissue, high heat is generated as the tissue absorbs the light. The cell membranes immediately rupture and proteins coagulate (denature), resulting in instant tissue death. However, the lower temperatures along the rim of this sphere-shaped process form a transition zone of injured cells that will die off within a few days. Meanwhile, in their death throes, they “release chemokines and different kinds of molecular danger signals”[iii] that recruit the immune system’s informants and killers.

Researchers from the Swedish device manufacturer Clinical Laserthermia Systems AB recently presented the results of experiments using mice inoculated with metastatic tumor cells. The mice were treated using FLA monitored by a temperature probe. Feedback from the probe was used to keep the temperature constant at 46°C for 30 minutes. According to their report, “This temperature has been shown to maximize the immunological response” while still assuring complete tumor coverage and ultimate destruction of all cancer cells.[iv] This was a very small study, and the research team acknowledges that more study and research is needed.

The abscopal effect has gained wide interest in cancer treatment and research, especially given its link with ablation. I believe that the more we learn about the post-ablation mediators for this effect, the more we will discover the role of FLA in stimulating it.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

[i] Seidi K, Zarghami N, Jahanban-Esfahlan R. Proposed approach for revealing unknown mediators of the abscopal effect. J Med Hypoth Ideas. 2013; 7(2):43-49
[ii] Abdo J, Cornell DL, Mittal SK, Agrawal DK. Immunotherapy Plus Cryotherapy: Potential Augmented Abscopal Effect for Advanced Cancers. Front Oncol. 2018; 8: 85.
[iii] Axelsson J, Pantaleone C, Astrom S. “Initial Findings of Immunostimulating of Interstitial Laser Thermotherapy of Solid Tumors.” Journal for Clinical Studies. 2017 Aug. Vol. 9, Issue 4. https://clinicallaser.se/wp-content/uploads/2017/08/AstromJCS.pdf
[iv] Axelsson J, Peterson K. Anti-tumor effects and immunological response following immune stimulating interstitial laser thermotherapy. Poster presentation. https://clinicallaser.se/wp-content/uploads/2017/11/SITC-Poster-2017.pdf

 

About Dr. Dan Sperling

Dan Sperling, MD, DABR, is a board certified radiologist who is globally recognized as a leader in multiparametric MRI for the detection and diagnosis of a range of disease conditions. As Medical Director of the Sperling Prostate Center, Sperling Medical Group and Sperling Neurosurgery Associates, he and his team are on the leading edge of significant change in medical practice. He is the co-author of the new patient book Redefining Prostate Cancer, and is a contributing author on over 25 published studies. For more information, contact the Sperling Prostate Center.

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