Uncovering the ways cancer manipulates immune cells

Cancer cells have a remarkable ability to reshape their surroundings to gain survival advantages. A developing tumor can, for instance, attract and reprogram immune white blood cells to help the tumor grow. Some of the co-opted immune cells, called macrophages, in turn release molecules that can both boost tumor growth and fend off other immune cells, such as cytotoxic T lymphocytes that would otherwise target and kill cancer cells.

Image: Three cytotoxic T lymphocytes surround a cancer cell (NIH)

Lisa Coussens, Ph.D., associate director of basic research for OHSU Knight Cancer Institute, is leading an effort to discover new therapies that block critical steps in the interactions between tumors and infiltrating immune cells. She will present recent results from her research at the first International Cancer Immunotherapy Conference, a sold-out event Sept. 16-19 in New York City.

Coordinated effort

With the explosion of interest in cancer immunotherapy and proliferation of scientific meetings, the field’s leaders decided the time is right for a coordinated effort. The American Association for Cancer Research, Association for Cancer Immunotherapy, Cancer Research Institute, and European Academy of Tumor Immunology are sponsoring the conference.

Lisa Coussens, Ph.D.
Lisa Coussens, Ph.D.

Coussens and her collaborators have uncovered several of the mechanisms behind immune cell manipulation by cancer. For instance, her team reported that inhibiting a key signaling pathway in macrophages, called CSF1R, interferes with macrophages co-opted by tumors and increases the number of cytotoxic T lymphocytes that infiltrate and kill cancer cells in mesotheliomas and cervical and breast carcinomas. In animal models, a CSF1R inhibitor decreased growth of these solid tumors and prevented their metastasis.

More recently, the group reported that macrophages infiltrating breast cancers are the significant source of a factor critical for regulating what cytotoxic T lymphocytes do in tumors, and how tumors respond to chemotherapy. Their data revealed a new target for drug intervention, and a possible biomarker for matching patients to specific immune therapies.

The Coussens lab also reported that it may be possible to make tumors more vulnerable to radiation therapy by blocking macrophages and select immune cells or immune-based pathways and similarly revealed that this therapeutic blockade significantly delayed tumor regrowth following radiotherapy.

Deep investment

The OHSU Knight Cancer Institute has made significant, long-term investments in immunotherapy research, including clinical trials that have led to FDA approved treatments.
Areas of focus include developing treatments for prostate, skin, breast, pancreatic, head and neck, thoracic and brain cancers. The institute is also studying immunotherapy for the treatment of some types of leukemia and other blood cell cancers.

The Knight Cancer Institute’s prostate program has been involved in the clinical development of cellular as well as antibody-based immunotherapies for more than a decade.

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Myeloid cells as targets for therapy in solid tumors by Tiziana Cotechini, Terry R. Medler, and Lisa M. Coussens; The Cancer Journal, July/August 2015.

Macrophages and therapeutic resistance in cancer by Brian Ruffell and Lisa M. Coussens; Cancer Cell, April 13, 2015.

Accessories to the crime: Functions of cells recruited to the tumor microenvironment by Douglas Hanahan and Lisa M. Coussens; Cancer Cell, March 20, 2012.