Assessing Chemo and Immunotherapy Biomarkers at the Right Time Seen as Crucial in Mesotheliomia Monitoring

The point at which doctors assess biomarkers of mesothelioma patients’ response to a combination of chemotherapy and immunotherapy is crucial to obtaining a clear picture of how the patients are doing, a study reports.

The same applies to other cancers, according to the study, which was published in BMC Cancer. A biomarker is a biological indicator of the presence or severity of a disease. A combination of chemotherapy and immunotherapy is called chemo-immunotherapy.

Researchers titled their study “Serial immunomonitoring of cancer patients receiving combined antagonistici anti-CD40 and chemotherapy reveals consistent and cyclical modulation of T cell and dendritic cell parameters.”

With an increasing number of immunotherapies in development, it is becoming increasingly important for scientists to identify biomarkers of their effectiveness, for two reasons. One is to identify patients most likely to benefit from treatment. Another is to see how patients respond to therapy.

CD40 is a tumor necrosis factor receptor — or cell signaling protein involved in inflammation — that immune cells express. Expression is the process by which information from a gene is used to create a functional product like a protein.

Helper T-cells that express CD40 are instrumental in activating a type of cell known as a CD8 cytotoxic T-cell. CD8 T-cells play a key role in the immune system shrinking tumors, a process known as tumor regression.

A combination of chemotherapy and an immunotherapy designed to activate cell signaling, such as the anti-CD40 antibody CP-870,893, may be effective against cancer. The combo has done a good job of treating advanced tumors in mice, studies have shown.

Researchers wanted to get a better handle on the immune changes the combo generates. They also wanted to identify biomarkers that could show patients were responding to the combo.

They gave 15 patients with mesothelioma up to six, 21-day cycles of Alimta (pemetrexed) plus Platinol (cisplatin) chemotherapy and an anti-CD40 antibody. The team analyzed patients’ blood samples weekly for a correlation between their immune-system characteristics and their overall survival.

Researchers found a correlation between higher than average proportions of two kinds of immune cells and overall survival. The cells were BDCA-2-positive dendritic cells and activated CD8 T-cells.

Another finding was that patients with higher than average BDCA-3-positive dendritic cells had poorer survival rates.

Researchers discovered that there were cyclical variations in immune cell populations during repeat cycles of chemo-immunotherapy. That prompted them to conclude that the timing of biomarker assessment was important to interpreting patients’ response to the combo over the course of treatment.

“Careful consideration of scheduling, consistency, and premedications is required in interpreting immunological change in chemo-immunotherapy trials,” the researchers wrote. “The availability of a control group is likely critical to robust interpretation of any potential biomarkers.”

 

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