How Can Immunotherapy Boost Focal Laser Ablation?

In the years since I first began treating localized prostate cancer using Focal Laser Ablation (FLA), I have acquired a broader perspective on cancer and the whole person. The human body contains an amazing defense mechanism with a “seek and destroy” mission against invasion from without and abnormality from within. It is called the immune system. Nature has equipped the immune system to protect us against outside invaders like viruses and bacteria. It is also designed to fight cancer, an internal attack from normal cells that have mutated into killers.

We have over 37 trillion cells in our bodies, each of them programmed to follow its normal span of existence as it performs its healthy function. However, mistakes do occur, leading to cell abnormalities. There are safety mechanisms that usually handle the situation but they’re not foolproof. Sometimes they fail, and a cancer cell is the result. This is where the immune system comes in.

Two components of the immune system might be thought of as characters in a spy novel: informants (dendritic cells or DCs) and assassins (killer T cells or TCs). The DCs throughout the body are vigilant spies, looking for abnormalities that are potential threats. When a DC encounters a suspicious cell, it registers and records the cell’s surface proteins called antigens. Just as a spy’s secret camera captures details that mark the suspect, the DC is now primed with intelligence to inform killer TCs. When a DC meets a TC, it says “If you run across a cell carrying this ID badge, take it out.” This activates the TC; it now has a mission to assassinate any suspects tagged with the same antigens.

Immunotherapy

Sometimes the TC’s mission aborts. Why? In keeping with the spy novel analogy, think of “assassin vs. assassin.” The TC has been primed with identifying intelligence from a DC—but after all, a lot of cells appear similar and the activated TC may kill normal cells by mistake. However, killer TCs have a checkpoint protein on them called PD-1. PD-1 regulates them so they don’t become overly ambitious. But cancer is also a killer, and one way to counter the killer TC is to wear a checkpoint protein disguise called PD-1L. When PD-1 binds with PD-1L, it shuts the TC down so it ignores the cancer cell. This is an immune evasion strategy that allows cancer to escape unharmed and proliferate.  

Now an exciting new area called immunotherapy offers promising alternatives to traditional cancer treatments like surgery, radiation, ablation, chemotherapy, etc. Such treatments are usually successful, especially if cancer is detected early, but they may have a price in terms of side effects—some permanent.

One principle of immunotherapy is the use of special drugs called checkpoint blockade drugs. In the type of sabotage involving checkpoint proteins, the countermeasure is to prevent PD-1 from binding with PD-1L so the TC isn’t fooled and will destroy the cancer cell. Cancer vaccines that disrupt binding are called checkpoint inhibitors. Although we aren’t at the point where these vaccines are curative, they may extend survival and even send tumors into remission (inactivity).

There is another immunotherapy principle, which is to directly strengthen DCs and TCs in order to make the checkpoint blockade more effective. An example of this is research being done through the Icahn School of Medicine at Mt. Sinai in New York. A paper published by Hammerich, et al. (2019)[i] describes an experimental immunotherapy for non-Hodgkin’s disease tumors. The treatment involves multiple steps that include 1) engineering DCs in order to “cross-present” antigens to TCs more effectively, 2) vaccination at the tumor site with a DC regulator to encourage DC multiplication, 3) briefly radiating the tumor to weaken it and force release of antigens for DCs to register, 4) and vaccination at the tumor site with a synthetic immune modulator. They hypothesized that they generated DCs that were then able to prime TC cells for greater potency and more efficient checkpoint blockade. Their results demonstrated significant tumor regression and extended survival.

The researchers note that their method may also activate a broader anti-tumor effect in the immune system, such that distant, non-vaccinated tumors from the same cancer also showed signs of regression. In the words of the authors, they were able to show “…that increasing and activating cross-presenting DC at the tumor site can prime tumor-specific TCs, restore efficacy of checkpoint blockade and yield superior antitumor immunity.”

Immunotherapy to boost FLA

To return to my focus on the whole person—and the immune system in each of us—my interest in applying immunotherapy to boost and preserve the effects of focal tumor ablation has rapidly grown. I am tracking research on how the immune system communicates within itself, how cells communicate with each other, and how biological and biochemical resources are being engineered and produced. I am particularly interested with the theory of immune vaccination into an ablation site or the surrounding area as a way to activate DCs and TCs to control microscopic cancer cells.

The more we are able to harness the body’s natural defense and healing processes, the greater the quality of life for patients. Immunotherapy has a bright future, and perhaps the day is not far off when cancer can not only be cured, but prevented.

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] Hammerich L, Marron TU, Upadhyay R, Svensson-Arvelund J et al. Systemic clinical tumor regressions and potentiation of PD1 blockade with in situ vaccination. Nat Med. 2019 Apr 8. doi: 10.1038/s41591-019-0410-x. [Epub ahead of print]

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