A new way to guide cancer immune therapy

Scrutinizing the immune cells infiltrating a tumor may reveal the cancer’s vulnerability or resistance to immune-based therapies.

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Cancer immune therapies have delivered life-saving, long-lasting results ­– but only in a fraction of patients, and clinicians have struggled to find a reliable way to identify the patients most likely to benefit. A new study shows that scrutinizing the kinds of immune cells that have infiltrated a tumor may reveal the cancer’s vulnerability or resistance to immune-based therapies, and perhaps improve treatment success.

Instead of focusing on one or two genes or proteins as biomarkers, the new method simultaneously evaluates a dozen characteristics of infiltrating immune cells in one sample from a biopsy or surgery, thus avoiding the major problem of limited quantities of tumor tissue. The researchers, led by OHSU Knight Cancer Institute investigator Lisa M. Coussens, Ph.D., describe the work in a paper published online today in the journal Cell Reports.

In archived samples from pancreatic cancer patients treated with GVAX, an immune therapy vaccine, the researchers found immune characteristics that correlated with response to treatment. Tumors heavily infiltrated by myeloid immune cells responded poorly to vaccination therapy, for instance, while survival was higher in patients with tumors infiltrated more heavily by activated CD8+ T cells, which responded more strongly to the therapeutic vaccine.

Figure 5 E
Kaplan-Meier analysis of neoadjuvant GVAX-treated pancreatic ductal adenocarcinoma cohort stratified by subgroups.

The finding that myeloid cells in tumors blunt anti-tumor immunity has implications for therapy. It highlights the potential for using myeloid antagonists in combination with vaccine or checkpoint-targeted immune therapy, said Coussens, who is associate director for basic research in the Knight Cancer Institute and professor and chair of the Department of Cell, Developmental and Cancer Biology in the OHSU School of Medicine.

Other researchers can readily use the new method in their own studies without significant cost, the authors said. It’s based on conventional immunohistochemistry staining of tissue preserved with formalin and embedded in paraffin wax, a common practice in medical laboratories. The authors also have released their computer code on GitHub, the popular web repository for hosting open-source software projects.

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Quantitative multiplex immunohistochemistry reveals myeloid-inflamed tumor-immune complexity associated with poor prognosis by Takahiro Tsujikawa, Sushil Kumar, Rohan N. Borkar, Vahid Azimi, Guillaume Thibault, Young Hwan Chang, Ariel Balter, Rie Kawashima, Gina Choe, David Sauer, Edward El Rassi, Daniel R. Clayburgh, Molly F. Kulesz-Martin, Eric R. Lutz, Lei Zheng, Elizabeth M. Jaffee, Patrick Leyshock, Adam A. Margolin, Motomi Mori, Joe W. Gray, Paul W. Flint, and Lisa M. Coussens. Cell Reports (April 4, 2017)