The Astounding Abscopal Effect - Systemic Anti Tumor Effects

What is the Abscopal Effect

The abscopal effect refers to the ability of localized radiation treatment of a tumor to have systemic antitumor effects. In the past, this has been rare and deemed almost a magical form of recovery. However, with continued developments in cancer research and immunotherapy strategies, this miraculous form of recovery is becoming more of a realistic possibility for cancer patients.
How does this work exactly? Previously, radiation therapy was used as a localized treatment focused on controlling and killing cancer tumor cells by direct damage while minimizing healthy tissue damage. However, as doctors are discovering, radiation therapy can elicit systemic antitumor effects by acting as an immunomodulator to the tumor microenvironment.

How Does Radiation Work

Radiation can act as an immunomodulator in several ways. By inducing cell death, radiation releases immunologic factors, one of which is improved antigen presentation to T cells. Radiation also causes local inflammation, which alerts the immune system. The immune system sends cells, including T cells, to the site of inflammation, where they encounter these antigens.
The antigens will then trigger the production of new antibodies that recognize the cancer cells as foreign. It is imperative because one of the reasons cancer is so hard to kill is that your body doesn’t recognize it as foreign and, therefore, won’t attack. Now, after radiation, these new antibodies travel through the body, and when they come across other cancerous tumors, they know to attack. However, it’s not perfect, and there are also negatives to radiation therapy.

Radiation Therapy Dangers

For example, it promotes certain cell types that fuel cancer growth. Not at the same speed as it kills cancer cells, but radiation can potentially promote:

1. TGF-b (transforming growth factor-beta) is a cytokine that is the protein used for signaling cell growth, proliferation, differentiation, and apoptosis. We certainly don’t want to promote these cytokines in areas with high levels of cancer cells.
2. MDSC (myeloid-derived suppressor cells) is a type of immune cell used to regulate the functions of specific immune cells, such as T cells, dendritic cells, macrophages, and natural killer cells. Cancer tissue with increased MDSC is more resistant to therapies and usually has a worse prognosis.
3. Regulatory T cells are a subpopulation of immunosuppressive T cells, which are good in normal tissue to help maintain tolerance to self-antigens and prevent autoimmune disorders. However, we don’t want to promote any immunosuppressive agent in areas of cancer growth.

So this means that to achieve the abscopal effect, doctors are using other immunotherapy agents in combination with radiation therapy to help combat these negative potential results. Doctors believe the abscopal impact will be much more attainable using radiation therapy and immunotherapy.

Immunotherapy, in this case, refers to targeted immunomodulatory drugs. For example, (generic names) Yervoy, Keytruda, Opdivo, Tecentriq, Bavencio, or Imfinzi may be given to patients undergoing radiation therapy. These drugs act mostly as checkpoint inhibitors. Checkpoint inhibitors block the normal proteins in cancer cells. When you block these proteins, T cells can attack the cancer cells that can no longer hide from the immune system.

Radiation and Immunotherapy

The ideal abscopal effect occurs when combining radiation therapy with immunotherapy. The combination therapies block checkpoint proteins and enhance other immunostimulatory signals. Specific immunostimulatory molecules that are released include:

1. Cytokines act as growth factors for dendritic cells, serving as messengers for the immune system by presenting antigens.
2. Cytokines, in the form of chemokines, play a vital role in cancer treatment by mobilizing the immune system. These molecules act as 'recruiters, 'guiding immune cells to the site of infection or inflammation, in this case, the cancerous tissue. Increased PD-L1 (programmed death ligand 1) helps induce apoptosis and, in this case, can synergistically work with radiation to reduce MDSCs.

This science still needs to be perfected, and everyone is different. There are many variables to consider, including what type of cancer a patient has and how their specific immune system will respond to treatments. Defining optimal radiation dosage, timing, and kind of immunotherapy drug is essential. Each case will be slightly different, and what works for someone may not work for another. The research is up-and-coming and can hopefully shed some light on future cancer treatments.

We hope this information has been helpful. Please feel free to contact us if you have any questions or feedback!