by Suzanne Bissonnette BSc MBA
The world of cancer treatment is constantly evolving, and one fascinating phenomenon, the abscopal effect, known for decades, recently returned to the forefront of research and drug development. This rare but promising occurrence could revolutionize how we approach cancer therapy, especially in the field of immunooncology [1].
What is the Abscopal Effect?
The abscopal effect is a unique phenomenon where localized treatment of a tumor, typically through radiation therapy, leads to the shrinkage of tumors elsewhere in the body. Recent reports of animal models in situ tumor treatment resulting in regression of both local and distant large tumors have been published [2]. Other preclinical and clinical work report local treatment triggering a systemic immune response that attacks cancer cells far from the original site. Could an abscopal effect be generated by immune checkpoint therapy, immune adjuvants, cellular therapy including CAR and NK cell therapies? Several ongoing clinical trials are evaluating those therapies [3].
Why does the abscopal effect matters in Immunooncology?
This effect is particularly interesting for immunooncology researchers because it suggests that:
Implications for Drug Development
The abscopal effect has significant implications for drug development:
Unexpected Observations and Potential Benefits
Interestingly, researchers sometimes observe the abscopal effect unexpectedly in phase I studies when using in situ tumor treatment. This serendipitous discovery has important implications for drug development as the observed effect could be leveraged to optimize dosing in phase II studies, potentially leading to reduced side effects because of lower yet effective doses. This approach could significantly improve the therapeutic index of cancer treatments, making them more tolerable for patients while maintaining or even enhancing efficacy [9].
While still rare, the abscopal effect offers a tantalizing glimpse into the potential of harnessing the body's own immune system to fight cancer more effectively. As research progresses, we may see new therapies that can reliably induce this effect, potentially transforming cancer treatment as we know it [10]. Finally, the ability to quantitatively predict and measure the abscopal phenomenon and its effects using technique such as radiomics scoring of CD8+ T cells may help researchers to standardize the evaluation of these new therapies/treatment regimens and their clinical outcomes for the benefit of patients [11].
References:
[1] Ngwa W, Irabor OC, Schoenfeld JD, Hesser J, Demaria S, Formenti SC. Using immunotherapy to boost the abscopal effect. Nat Rev Cancer. 2018 May;18(5):313-322.
[2] Furong Cheng et al. Single-dose injectable nanovaccine-in-hydrogel for robust immunotherapy of large tumors with abscopal effect. Sci. Adv. 2023 Jul 14; 9(28):ade6257
[3] Nelson BE, Adashek JJ, Lin SH, Subbiah V. The abscopal effect in patients with cancer receiving immunotherapy. Med. 2023 Apr 14;4(4):233-244.
[4] Demaria S, Ng B, Devitt ML, Babb JS, Kawashima N, Liebes L, et al. Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated. Int J Radiat Oncol Biol Phys. 2004 Mar 1;58(3):862-870.
[5] Formenti SC, Demaria S. Systemic effects of local radiotherapy. Lancet Oncol. 2009 Jul;10(7):718-726.
[6] Weichselbaum RR, Liang H, Deng L, Fu YX. Radiotherapy and immunotherapy: a beneficial liaison? Nat Rev Clin Oncol. 2017 Jun;14(6):365-379.
[7] Deutsch E, Chargari C, Galluzzi L, Kroemer G. Optimizing efficacy and reducing toxicity of anticancer radioimmunotherapy. Nat Rev Clin Oncol. 2019 Jan;16(1):32-48.
[8] Demaria S, Formenti SC. Can abscopal effects of local radiotherapy be predicted by modeling T cell trafficking? J Immunother Cancer. 2016 May 17;4:29.
[9] Marabelle A, Tselikas L, de Baere T, Houot R. Intratumoral immunotherapy: using the tumor as the remedy. Ann Oncol. 2017 Dec 1;28(suppl_12):xii33-xii43.
[10] Grass GD, Krishna N, Kim S. Immunotherapeutic approaches for hepatocellular carcinoma. Oncotarget. 2016 Aug 23;7(34):54699-54710.
[11] Sun R, Sundahl N, Hecht M, et al. Radiomics to predict outcomes and abscopal response of patients with cancer treated with immunotherapy combined with radiotherapy using a validated signature of CD8 cells. Journal for ImmunoTherapy of Cancer 2020;8:e001429. doi: 10.1136/jitc-2020-001429
