Potential of memory T cells in bridging preoperative chemoradiation and immunotherapy in rectal cancer
| Autor: | Mark De Ridder, Joeri L. Aerts, Olivier Feron, Sven de Mey, Inès Dufait, Heng Jiang, Hui Wang, Valeri N. Verovski, Thierry Gevaert, Benedikt Engels |
|---|---|
| Přispěvatelé: | UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Oncology medicine.medical_specialty Colorectal cancer medicine.medical_treatment Antineoplastic Agents Disease CD8-Positive T-Lymphocytes Memory T cells law.invention 03 medical and health sciences 0302 clinical medicine Randomized controlled trial law Internal medicine Preoperative Care medicine Humans Radiology Nuclear Medicine and imaging Rectal cancer Neoplasm Staging Rectal Neoplasms business.industry TOR Serine-Threonine Kinases IL-2 Chemoradiotherapy Off-Label Use Hematology Immunotherapy medicine.disease Warburg effect Total mesorectal excision Neoadjuvant Therapy Metformin Treatment Outcome 030104 developmental biology Clinical research 030220 oncology & carcinogenesis Colonic Neoplasms mTOR Tumor Escape Radiotherapy Intensity-Modulated business Adjuvant |
| Zdroj: | Radiotherapy & Oncology, (2018) |
| ISSN: | 0167-8140 |
| DOI: | 10.1016/j.radonc.2018.04.003 |
| Popis: | The management of locally advanced rectal cancer has passed a long way of developments, where total mesorectal excision and preoperative radiotherapy are crucial to secure clinical outcome. These and other aspects of multidisciplinary strategies are in-depth summarized in the literature, while our mini-review pursues a different goal. From an ethical and medical standpoint, we witness a delayed implementation of novel therapies given the cost/time consuming process of organizing randomized trials that would bridge an already excellent local control in cT3-4 node-positive disease with long-term survival. This unfortunate separation of clinical research and medical care provides a strong motivation to repurpose known pharmaceuticals that suit for treatment intensification with a focus on distant control. In the framework of on-going phase II-III IG/IMRT-SIB trials, we came across an intriguing translational observation that the ratio of circulating (protumor) myeloid-derived suppressor cells to (antitumor) central memory CD8+ T cells is drastically increased, a possible mechanism of tumor immuno-escape and spread. This finding prompts that restoring the CD45RO memory T-cell pool could be a part of integrated adjuvant interventions. Therefore, the immunocorrective potentials of modified IL-2 and the anti-diabetic drug metformin are thoroughly discussed in the context of tumor immunobiology, mTOR pathways and revised Warburg effect. |
| Databáze: | OpenAIRE |
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