BC Cancer Agency researchers have discovered that the number of macrophages – a type of white blood cell that normally scavenges foreign material – found in a patient’s tumour had a strong correlation to treatment outcome. The greater the number of macrophages; the greater the likelihood of a relapse.
Hodgkin lymphoma is a cancer of lymphocytes which typically affects young adults, but can occur at any age. It is a highly treatable form of cancer, with about 75 to 85 percent of patients cured with initial treatment. However, if the first therapy fails, secondary treatment usually includes a bone marrow transplant, which is only successful for about one-half of these cases.
“The study demonstrates that high numbers of macrophages are associated with treatment resistance in Hodgkin lymphoma suggesting a way to identify the 25 percent of patients who currently don’t respond well,” says Dr. Joseph Connors, one of the study researchers and clinical director of the BC Cancer Agency’s Centre for Lymphoid Cancer.
Researchers tested 130 tissue samples of patients who had received standard treatment therapies. Of the 130 patients, 92 were cancer free but 38 had experienced a relapse. Using high-throughput genomic techniques, researchers looked at almost 30,000 genes to search for associations between gene expression and treatment outcomes. When the researchers looked back at the original biopsies of the patients whose treatment ultimately failed they found a group of genes typically expressed by normal macrophages to be markedly overexpressed.
“We haven’t appreciated the important role that macrophages may play in cancer development before now,” says Christian Steidl, lead author and researcher at the BC Cancer Agency’s Centre for Lymphoid Cancer, “Macrophages have been primarily considered the scavengers of the body, as they normally eat and ingest the debris that the body wants to eliminate. But, in some patients with Hodgkin lymphoma, the macrophages can be subverted to misdirect the immune system, creating a haven in which the malignant cells can safely hide.”
To validate their discovery, researchers stained the tissue samples of another 163 patients and found a close correlation between the number of macrophages and the outcome of primary treatment. Patients whose tissue samples had a higher number of macrophages were also much less likely to have a good outcome after receiving secondary treatment, such as a bone marrow transplant, strongly suggesting that macrophage content can be used to predict success or failure for both primary and secondary treatments.
“This is an important discovery because it could, in the future, give us a biomarker to help predict who may or may not do well with current therapies,” says BC Cancer Agency pathologist, scientist and senior author Dr. Randy Gascoyne. “We could then justify recommending more intense or experimental treatments knowing that standard treatment is likely to fail.
“We could also reduce the future risk that Hodgkin lymphoma patients – who are often very young when diagnosed – will develop secondary cancers related to treatment toxicity by providing less intense therapy when biopsy results display few macrophages.”
The research was conducted with funding from the Canadian Institutes of Health Research with additional funding from BC Cancer Agency Centre for Lymphoid Cancer, the Michael Smith Foundation for Health Research, the Lymphoma Research Foundation, and the Cancer Research Society of Canada.
The BC Cancer Agency, an agency of the Provincial Health Services Authority, is committed to reducing the incidence of cancer, reducing the mortality from cancer, and improving the quality of life of those living with cancer. It provides a comprehensive cancer control program for the people of British Columbia by working with community partners to deliver a range of oncology services, including prevention, early detection, diagnosis and treatment, research, education, supportive care, rehabilitation and palliative care. The BC Cancer Foundation raises funds to support research and enhancements to patient care at the BC Cancer Agency. www.bccancer.bc.ca
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