European Conference on Interventional Oncology

April 28 - May 1 | Palma de Mallorca, ES

April 28 - May 1 | Palma de Mallorca, ES

April 28 - May 1 | Palma de Mallorca, ES

April 28 - May 1 | Palma de Mallorca, ES

April 28 - May 1 | Palma de Mallorca, ES

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ProgrammeIntraarterial therapies for priming the immune system: rationale and clinical results

Intraarterial therapies for priming the immune system: rationale and clinical results

 

Three reasons why you cannot miss my lecture:

  • We will discuss the rationale and mechanisms for using transarterial therapy for priming the immune system
  • You will understand why combining immunotherapy and transarterial therapy may prove beneficial to treat solid organ malignancy
  • I will highlight the results of the most recent clinical trials that combine immunotherapy and transarterial therapy

Prof. David Madoff
Speaker bio
 

Click here to watch this lecture via the ECIO 2023 congress platform.

Interventional oncologists (IOs) are playing an ever-increasing role in the management of various types of solid tumors. In fact, numerous in situ tumor destruction techniques (e.g., percutaneous ablation, transarterial therapy, radiation therapy, etc.) can successfully kill tumors, lead to increased overall survival and result in an improved quality of life. [1] While good results have been seen in patients with early-stage disease or in those with oligometastases, outcomes for patients with advanced disease remain poor.

Immunotherapy also has an important role in the management of malignant tumors. Despite the recent improvements of systemic chemotherapy and biologics, immune checkpoint inhibitors have yielded promising clinical applications. It has now been shown that monotherapy only benefits some patients. Therefore, combinations of immune checkpoint inhibitors with different mechanisms of action have been used with agents targeting programmed cell death protein 1 (PD-1) & cytotoxic lymphocyte-associated antigen 4 (CTLA-4). This has been shown to significantly increase overall response rates and overall survival in patients with malignant melanoma. [2] Unfortunately, these combined therapies increase the incidence of immune-related adverse events. [3] Therefore, it has become necessary to adopt a comprehensive treatment strategy based on immune checkpoint inhibitors that can then both increase overall response rates and reduce treatment-related adverse events. [4]

In recent years, there has been substantial interest in stimulating the immune system to reduce local tumor recurrence and the development of distant metastases by utilizing various locoregional therapies. The immune system and its interactions with locoregional therapies is very complex and there are numerous ways that each targeted therapy contributes to the interplay with the immune system. The locoregional therapies are typically used to treat the primary tumor and they have specific immunomodulatory responses that can then be stimulated or suppressed based on the mechanism of action of the chosen immunotherapy. In fact, IOs have been using immunotherapeutic strategies for more than two decades that combine transarterial embolotherapy with an immunostimulant drug (e.g., interferon, GM-CSF, OK-432, etc.). This approach, called immuno-embolization, was found in patients with HCC [5] and uveal melanoma metastases [6] to be reasonably effective at stimulating an immune response at off-target sites but resulted in less tumor necrosis in the target tumor than standard chemoembolization (TACE) approaches.

We now know that transarterial therapies such as TACE and transarterial radioembolization (TARE) have both immunostimulatory and immunosuppressive effects. [7] Transarterial approaches are used to achieve necrosis of the tumor tissue, reduce the release of immunosuppressive factors, and alter peripheral immune cell phenotypes while reducing the number of peripheral T helper cells and induce a hypoxic microenvironment. They can also upregulate HIF-1α and PD-L1 expression and damage the normal liver tissue. On the other hand, ablative therapies can stimulate the immune system by reducing immunosuppression, increasing the exposure of tumor antigens and enhances the immunogenicity of tumor antigens, active antigen presenting cells and increase tumor-specific T cells while suppressing the immune system by increase the production of IL-6, HIF-1α,HGF and its receptor c-MET and upregulating PD-L1 expression. Lastly, like brachytherapy I125 seeds, TARE can act to induce in situ vaccination and re-program the tumor microenvironment while increasing PD-L1 expression and infiltration of Treg into the tumor microenvironment. Based on some positive results from locoregional therapies and immune checkpoint inhibitors in HCC, separately, many clinical trials have been initiated to test the combination of immune checkpoint blockade (and other types of immunotherapy) plus locoregional therapies.

This talk will, therefore, introduce the rationale for using transarterial therapies to prime the immune system and allow the audience to understand the various specific immune change that will be induced by transarterial therapies. [8,9] Furthermore, the mechanisms of immune stimulation with the various intra-arterial therapies and the available data on immune system stimulation with intra-arterial therapies will be reviewed. [10,11]

 

David Madoff

Yale School of Medicine, New Haven, US

Prof. David Madoff is Professor of Radiology, Medical Oncology and Surgical Oncology, Vice Chair for Clinical Research, Section Chief of Interventional Radiology and co-Director of the IO Research Lab at Yale School of Medicine. He is an internationally recognized expert in interventional oncology and treats cancer patients with transarterial and ablative approaches in the liver and other organ systems such as lung, kidney and bone. Prof. Madoff is a leader in academic radiology and has been an invited speaker at numerous national and international meetings. He authored or co-authored over 180 peer-reviewed scientific articles, has written more than 30 book chapters and served as co-editor of four textbooks. Prof. Madoff served as Deputy Editor for RADIOLOGY and JVIR, and is currently co-Editor-in-Chief of Digestive Disease Interventions. He currently serves on the editorial boards of Techniques of Vascular and Interventional Radiology, Seminars in Interventional Radiology, Current Oncology Reports, Chinese Clinical Oncology and Cancer Biology and Medicine. Prof. Madoff is active in many major radiological societies including RSNA, ARRS, SIR, SIO, CIRSE and AUR and serves on the Board of Trustees of the ARRT. Based on his important contributions to the field, Prof. Madoff was elected Fellow of SIR in 2007, ACR in 2015 and CIRSE in 2017.

 

References

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  2. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, Ferrucci PF, Hill A, Wagstaff J, Carlino MS, Haanen JB, Maio M, Marquez-Rodas I, McArthur GA, Ascierto PA, Long GV, Callahan MK, Postow MA, Grossmann K, Sznol M, Dreno B, Bastholt L, Yang A, Rollin LM, Horak C, Hodi FS, Wolchok JD. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med 2015 Jul 2;373(1):23-34. doi: 10.1056/NEJMoa1504030. Epub 2015 May 31.
  3. Hodi FS, Chesney J, Pavlick AC, Caroline R, Grossman KF, McDermott DF, Linette GP, Meyer N, Giguere JK, Agarwala S, Shaheen M, Ernstoff MC, Minor DR, Salama AK, Taylor MH, Ott PA, Horak C, Gagnier P, Jian J Wolchok, JD, Postow MA. Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. Lancet Oncol. 2016. PMID: 27622997.
  4. Salama AK, Moschos SJ. Next steps in immuno-oncology: enhancing antitumor effects through appropriate patient selection and rationally designed combination strategies. Ann Oncol 2017 Jan 1;28(1):57-74. doi: 10.1093/annonc/mdw534.
  5. Kenjo A, Sato T, Marubashi S, Saito T, Tsuchiya T, Kimura T, Sato N, Takahashi A, Ohira H, Gotoh M. Role of intratumoral infiltrating macrophages after transarterial immunoembolization for hepatocellular carcinoma. J Hepatobiliary Pancreat Sci. 2016 May;23(5):298-304. doi: 10.1002/jhbp.342. Epub 2016 Apr 4. PMID: 26946336
  6. Yamamoto A, Chervoneva I, Sullivan KL, Eschelman DJ, Gonsalves CF, Mastrangelo MJ, Berd D, Shields JA, Shields CL, Terai M, Sato T. High-dose immunoembolization: survival benefit in patients with hepatic metastases from uveal melanoma. Radiology. 2009 Jul;252(1):290-8. doi: 10.1148/radiol.2521081252.
  7. Zeng P, Shen D, Zeng CH, Chang XF, Teng GJ. Emerging Opportunities for Combining Locoregional Therapy with Immune Checkpoint Inhibitors in Hepatocellular Carcinoma. Curr Oncol Rep. 2020 Jun 29;22(8):76. doi: 10.1007/s11912-020-00943-6.
  8. Lucatelli P, Iezzi R, De Rubeis G, Goldberg SN, Bilbao JI, Sami A, Akhan O, Giuliante F, Pompili M, Tagliaferri L, Valentini V, Gasbarrini A, Colosimo C, Bezzi M, Manfredi R. Immuno-oncology and interventional oncology: a winning combination. The latest scientific evidence. Eur Rev Med Pharmacol Sci 2019 Jun;23(12):5343-5350.
  9. Erinjeri  JP, Fine GC, Adema GJ, Ahmed M, Chapiro J, den Brok M, Duran R, Hunt SJ, Johnson DT, Ricke J, Sze DY, Toskich BB, Wood BJ, Woodrum D, Goldberg SN. Immunotherapy and the Interventional Oncologist: Challenges and Opportunities-A Society of Interventional Oncology White Paper. Radiology 2019 Jul;292(1):25-34. doi: 10.1148/radiol.2019182326. Epub 2019 Apr 23.
  10. Valery M, Cervantes B, Samaha R, Gelli M, Smolenschi C, Fuerea A, Tselikas L, Klotz-Prieux C, Hollebecque A, Boige V, Ducreux M. Immunotherapy and Hepatocellular Cancer: Where Are We Now? Cancers (Basel) 2022 Sep 19;14(18):4523. doi: 10.3390/cancers14184523.
  11. Salem R, Greten TF. Interventional radiology meets immuno-oncology for hepatocellular carcinoma. J Hepatol 2022 Aug 19:S0168-8278(22)03003-3. doi: 10.1016/j.jhep.2022.08.003.