Facebook
Twitter
LinkedIn
Email
 |
Checking for direct PDF access through Ovid | |
Excerpt
‘New insights into the microenvironment of tumours point to the need for treatments that target interaction between tumours and the normal cells around them, something that is especially true for haematologic malignancies’
This is particularly true for haematological malignancies, said Dr Randy Gascoyne, a haematopathologist with the British Columbia Cancer Agency and Clinical Professor of Pathology & Laboratory Medicine at the University of British Columbia.
‘Haematology research into the microenvironment has lagged behind microenvironmental research in solid tumours’, he said, in the Henry Rappaport Memorial Lecture at the International Conference on Malignant Lymphoma.
For many years, lymphoma research had concentrated on understanding genetic alterations in neoplastic cells, particularly the malignant B cell, he said. But in more recent years, attention has turned to the composition and function of non-neoplastic cells in the tumour microenvironment, defined as all non-neoplastic cells and stromal components in the immediate vicinity of the tumour cells.
The interaction between a tumour and its microenvironment can aid the tumour's development. For example, crosstalk between neoplastic B cells and microenvironmental tumour-associated macrophages can subvert immune response, fail to present tumour antigens to cytotoxic T cells, and promote immature dendritic cells, Dr Gascoyne said.
‘It may even be that follicular lymphoma can be divided into two major groups - one driven largely by tumour cell genetics and the other by microenvironmental interactions.
‘We have to identify biomarkers that identify these subsets. Within follicular lymphoma and diffuse large B-cell lymphoma, for example, a percentage of cases have lots of blood vessels, and those are probably the subgroup who are truly going to benefit from the Avastin trial that Roche is doing right now.’
Non-neoplastic cells implicated in the microenvironment of several non-Hodgkin-lymphoma subtypes and in many solid tumours include reactive T cells, regulatory T cells, benign B cells, macrophages, dendritic cells, fibroblastic reticular cells, and endothelial cells that comprise the vascular bed of these tumours, he said.
The importance of these non-neoplastic cells is illustrated by the fact that follicular lymphoma cells are almost impossible to grow in-vitro and show a strong dependency on both stromal and immune-related cells, he noted.
There are treatments today that aim at the microenvironment, ‘but we are not following a paradigm that allows us to treat those groups. We treat patients with diffuse large B-cell lymphoma and then try to dissect out the subgroup that benefits from our treatments.
