Can you think of a time when you experienced an unexpected negative occurrence from some decision or action on your part? Hopefully it wasn’t a huge impact and was easily corrected. However, history is littered with large-scale tragedies stemming from what seemed like a good idea at the time. For example, Chairman Mao’s campaign to eliminate the sparrows that ate agricultural seeds, thus diminishing food crops. However, the birds’ diet was based far more on insects than seeds, and once they were gone, locusts overran the grain fields, leading to 45 million deaths due to famine.

On the other hand, decisions and actions can lead to unintended positive consequences. In ancient Rome, this was called a felix culpa or happy fault, often attributed to luck. In the field of medicine, many discoveries have been lucky accidents, bringing unexpected positive outcomes from a drug or treatment intended for something else.

A good example of this is something that started to show up in the 1960’s and 1970’s, when interventions were being developed as alternatives to invasive surgeries. You may not be familiar with the name Dr. Richard Ablin, but you are certainly familiar with the PSA blood test. It was Dr. Ablin, a pathologist, who discovered PSA (prostate specific antigen) in 1970. Although others devised the PSA blood test as a screening method for prostate cancer, it would not have been possible if it weren’t for Dr. Ablin. That same year, Ablin co-authored a journal article describing how some metastatic prostate cancer patients appeared to go into remission following ablation of their prostate tumor using cryotherapy (freezing).^[i] The authors theorized how cellular destruction had a positive biologic consequence of mobilizing the immune system. Even though that’s not what they intended, it was truly a felix culpa.

Closer to our own time, an authority in immunopharmacology (immunotherapy drugs) published a paper with the technical title, “Tumor abolition and antitumor immunostimulation by physico-chemical tumor ablation.”^[ii] Professor Yona Keisari (Tel Aviv University) writes that all methods of focal tumor ablation, including Focal Laser Ablation (FLA), have been observed to result in “systemic anti-tumor reactions.” This means that destroying a single tumor mobilizes the entire immune system in the patient’s body to tackle other tumor cells (from the same cancer) in any location.

As Keisari describes it, specialized immune system cells called juvenile dendritic cells flock to the inflamed area immediately after the ablation. There, they are exposed to specific molecules from the damaged cancer cells. These molecules that act as a kind of ID tag, or biomarker. The juvenile dendritic cells internalize these tumor-specific biomarkers. Then, as the juvenile cells mature and circulate throughout the body, when they encounter the immune system’s killer T cells, they “present” these biomarkers to the T cells, which then perform a seek-and-destroy mission to kill any cancer cell with the same biomarkers.

This ability of the immune system to identify the hostile cells and recognize them wherever they find them is a positive unintended consequence of something that was designed just to demolish a one tumor in a single location. The trouble is, while it may occur naturally in one patient, it may not in another. It’s not predictable who will or won’t have this organic response.

Professor Keisari offers a possibility: The potential property of ablation to stimulate a system wide attack on cancer “…could portend a future collaboration with immunotherapeutic procedures.” To put it a different way, integrating a focal ablation with immunotherapy drugs may unite body’s native abilities together with pharmaceuticals in a way that each amplifies the effect of the other. If so, it would be a positive intended consequence—hopefully with no negative surprises.

To sum up, FLA joins other types of thermal or chemical ablation in acting as an agent that calls the immune system into action, and programs it to target tumor specific cells in circulation or colonization elsewhere. For example, the response has been observed in HIFU (High Intensity Focused Ultrasound) cases. In a 2018 article by Mauri, et al, the authors note a positive unintended consequence: “One of the most fascinating aspects of image-guided ablations, and particularly of HIFU, is the reported possibility of determining a sort of stimulation of the immune system, with an unexpected ‘systemic’ response to treatments designed to be ‘local’.”^[iii] When fortified by today’s (and tomorrow’s) immunotherapies, it may be an unbeatable combination.

For more information about the Sperling Prostate Center’s image-guided ablation methods (FLA, TULSA-PRO, and Exablate MR-guided HIFU), contact us today.

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.

References

[i] W.A. Soanes, R.J. Ablin, M.J. Gonder, Remission of metatatic lesions following cryosurgery in prostatic cancer: immunologic considerations, Journal of Urology 104 (1970) 154–159
[ii] Keisari Y. Tumor abolition and antitumor immunostimulation by physico-chemical tumor ablation. Front Biosci (Landmark Ed). 2017 Jan 1;22(2):310-347.
[iii] Mauri G, Nicosia L, Xu Z, Di Pietro S et al. Focused ultrasound: tumour ablation and its potential to enhance immunological therapy to cancer. Br J Radiol. 2018 Feb;91(1083):20170641.