Tumor-derived dendritic cells to slow tumor growth

Cancer is among the leading causes of death worldwide, in part due to the lack of effective therapies. However, 90% of all cancer related deaths, result from the development of metastasis or relapse and treatments specifically targeting these phenomena are currently lacking. Therefore, there is an urgent medical need of new treatments for cancer and metastasis, whereby the side effects of conventional therapies (such as chemotherapy) are avoided or at least reduced.


Besides cancer cells, the tumor microenvironment (TME) contains a large array of non-cancerous cell types, including innate and adaptive immune cells. Many of these immune cells are suppressed in the TME and cannot perform their anti-tumor functions properly. However, we discovered that multiple mouse tumors as well as human tumors harbor two specific types immune cells, namely conventional dendritic cells (cDCs), with anti-tumoral properties. Both tumor-derived cDC subsets have lymph node migratory potential, whereby cDC1s efficiently activate CD8+ T cells and cDC2s induce Th17 cells. Interestingly, both tumor-derived DC subsets can be used to elicit therapeutically relevant immune responses in cancer when used as an “anti-cancer” vaccine. As such, mice vaccinated with tumor-derived cDC2s displayed a reduced tumour growth accompanied by a reprogramming of pro-tumoural tumor-associated macrophages (TAMs), while cDC1 vaccination strongly induces anti-tumour cytotoxic T lymphocytes (CTLs).


The findings of our research suggest a new approach in which DCs are isolated from surgically-removed tumors from patients and can be used to “vaccinate” this same patient in slowing tumor growth or potentially metastatic relapses. Hence, we have discovered a potential new personalized immunotherapy, which makes use of the patient’s own immune system to avoid cancer relapse and metastasis.

Authors

Damya Laoui (1,2)
Jiri Keirsse (1,2)
Martin Guilliams (3,4)
Jo Van Ginderachter (1,2)

Organisations

Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium (1)
Laboratory of Myeloid Cell Immunology, VIB Center for Inflammation Research, Brussels, Belgium (2)
Unit of Immunoregulation and Mucosal Immunology, VIB Inflammation Research Center, 9000 Ghent, Belgium (3)
Department of Biomedical Molecular Biology, Ghent University, 9000 Ghent, Belgium (4)

Presenting author

Damya Laoui, Post-doctoral fellow, VIB-VUB
dlaoui@vub.be
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