Immunomodulatory Effects of Stereotactic Body Radiotherapy and Vaccination with Heat-Killed Mycobacterium Obuense (IMM-101) in Patients with Locally Advanced Pancreatic Cancer
| العنوان: | Immunomodulatory Effects of Stereotactic Body Radiotherapy and Vaccination with Heat-Killed Mycobacterium Obuense (IMM-101) in Patients with Locally Advanced Pancreatic Cancer |
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| المؤلفون: | Freek R. van ‘t Land, Sai P. Lau, Willem de Koning, Larissa Klaase, Madelief Vink, Anneloes van Krimpen, Jasper Dumas, Disha Vadgama, Joost J. Nuyttens, Dana A. M. Mustafa, Ralph Stadhouders, Marcella Willemsen, Andrew P. Stubbs, Joachim G. Aerts, Casper H. J. van Eijck |
| المساهمون: | Surgery, Pathology, Pulmonary Medicine, Radiotherapy, Cell biology |
| المصدر: | Cancers, 14(21):5299. Multidisciplinary Digital Publishing Institute (MDPI) Cancers; Volume 14; Issue 21; Pages: 5299 |
| بيانات النشر: | MDPI AG, 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Cancer Research, SDG 3 - Good Health and Well-being, Oncology, pancreatic ductal adenocarcinoma (PDAC), locally advanced pancreatic cancer (LAPC), stereotactic body radiotherapy (SBRT), mycobacterium vaccines, cancer immunotherapy, immuno-oncology |
| الوصف: | Background: Patients with locally advanced pancreatic cancer (LAPC) are treated with chemotherapy. In selected cases, stereotactic body radiotherapy (SBRT) can be added to the regimen. We hypothesized that adding an adjuvant containing a heat-killed mycobacterium (IMM-101) to SBRT may lead to beneficial immuno-modulatory effects, thereby improving survival. This study aims to investigate the safety of adding IMM-101 to SBRT and to investigate the immuno-modulatory effects of the combination treatment in the peripheral blood of LAPC patients. Methods: LAPC patients were treated with SBRT (40 Gy) and six intradermal vaccinations of one milligram IMM-101. The primary endpoint was an observed toxicity rate of grade 4 or higher. Targeted gene-expression profiling and multicolor flow cytometry were performed for longitudinal immune-monitoring of the peripheral blood. Results: Twenty patients received study treatment. No treatment-related adverse events of grade 4 or higher occurred. SBRT/IMM-101 treatment induced a transient decrease in different lymphocyte subsets and an increase in CD14+CD16−CD11b+HLA−DRlow myeloid-derived suppressor cells. Importantly, treatment significantly increased activated ICOS+, HLA-DR+ and Ki67+PD1+ T and NK cell frequencies. This was not accompanied by increased levels of most inhibitory markers, such as TIM-3 and LAG-3. Conclusions: Combination therapy with SBRT and a heat-killed mycobacterium vaccine was safe and had an immune-stimulatory effect. |
| وصف الملف: | application/pdf |
| تدمد: | 2072-6694 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3809ecb30078debd9f5ae7c3530cdd41Test https://doi.org/10.3390/cancers14215299Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3809ecb30078debd9f5ae7c3530cdd41 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20726694 |
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