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Tumor Infiltrating Myeloid Cell Compartment

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Immune cells in the tumour microenvironment

Mechanisms underlying the interaction of immune cells with tumour cells in their microenvironment are still obscure. A European consortium developed strategies to understand and manipulate interactions of particular classes of immune cells with the developing tumours.

Fundamental Research
Health

Recent research on tumour-associated myeloid cells attracted particular attention because their presence in tumours is often linked to poor patient survival. Experimental studies indicated that myeloid cells modulate key cancer-associated activities including immune evasion, and affect all types of cancer therapy. These cells form the tumour infiltrating myeloid cell compartment (TIMCC), preventing more specific immune cells from entering the tumour microenvironment (TME) and acting as tumour killers. It is possible that the tumour hijacks the myeloid cells to protect itself against attacks from other immune cells, or the immune system starts to consider the tumour as a wound that needs healing. Consequently, targeting myeloid cells could overcome limitations of current treatment options. The EU-funded TIMCC (Tumour infiltrating myeloid cell compartment) consortium brought together eight expert teams within immunology, genetics and oncology disciplines to provide methodological training and determine the role of TIMCC in cancer. Researchers of this training network isolated and characterised individual myeloid cells from a variety of treated and untreated human and mouse tumours. The TIMCC appeared as a very heterogeneous cell population with a pro-tumour and immune-suppressive signature. Corresponding experimental models of human tumours showed comparable patterns of TIMCC cell population. Depletion of some subpopulations of myeloid cells from tumour bearing mice improved the efficacy of chemotherapy, proving that these cells represent potential targets in combination therapy. However, in some tumour models, myeloid cells were indispensable for therapeutic efficacy, illustrating the complexity of the system. In particular, mouse models lacking a specific subtype of myeloid cells, the mast cell, demonstrated that they have no role in tumour development despite their presence in the TME. The results of the project indicate that the TIMCC has a strong impact on the outcome of cancer immunotherapy. The TIMCC training and research programme successfully educated a team of young researchers by providing multidisciplinary biomedical knowledge, skills and key insights on the complexity of translational medicine.

Keywords

Tumour microenvironment, tumour-associated myeloid cells, TIMCC, cancer immunotherapy, translational medicine

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