Inflammation and Cancer Research

Researchers at Fox Chase Cancer Center discuss their lab’s focus on the role inflammation plays in the initiation and progression of cancer.

inflamation

Pictured from left to right: Glenn Rall, Kerry Campbell, Sergei Grivennikov, and Ekaterina Koltsova. Not pictured: Siddharth Balachandran and Zeng-jie Yang. Photo courtesy of Paul Reitano.

Q: Dr. Rall, can you start by talking about your research?

Glenn F. Rall, PhD: Fox Chase has a long history of understanding how “normal” processes work so that we can more fully capture what goes wrong in particular diseases, such as cancer. My current work is focused on understanding the cellular and organ contexts that dictate whether the host response is protective or damaging, which is key to developing antiinflammatory strategies for both solid tumors and brain disease. It may be especially relevant in CNS tumors.
Siddharth Balachandran, PhD: Our laboratory is identifying how interferons activate an immune-stimulatory form of death in cancer cells. Such death will not only be expected to directly shrink the tumor, but it will also activate an immune response to the tumor, allowing its subsequent clearance by combinatorial immunotherapeutic approaches.
Sergei Grivennikov, PhD: We have defined inflammatory cytokines as key pieces connecting chronic inflammation to increased tumor growth in cancers, where long-term chronic inflammation precedes and predisposes to cancer development. We also contributed to the introduction of the “tumor-elicited inflammation” concept—a first appreciation that most of the solid tumors have upregulated inflammatory responses that aid tumor growth.

Q: Dr. Yang, can you describe your research on inflammation and medulloblastoma?

Zeng-jie Yang, MD, PhD: We’ve found that immune cells, including macrophages and neutrophils, represent the major component of tumor microenvironment in medulloblastoma. Moreover, the inflammatory molecules, such as interleukins and TNF-alpha, appear to be critical for tumor growth. We want to elucidate how these inflammatory cells are recruited and how they interact with tumor cells to promote tumor cell propagation.

Q: Dr. Campbell, what is most promising about your research?

Kerry S. Campbell, PhD: We’ve analyzed the status of immune cells (NK cells, T cells, monocytes) using flow cytometry. Those studies revealed that immune status differs substantially in patients with distinct cancers. A recent study of patients with renal cell carcinoma found that NK cells, T cells, and monocytes exhibit significantly increased expression of an inhibitory receptor called PD-1, which is known to suppress these immune cells. Surprisingly, surgical removal of the tumor resulted in rapid loss of the PD-1–expressing cells.

Q: What are the implications of that finding, given the popularity of two new immunotherapeutic antibodies (pembrolizumab and nivolumab) that block PD-1 to restore immune function?

Campbell: Our data suggest that these antibodies may not be effective after surgical excision of the primary tumor, since PD-1 is no longer expressed in most patients.

Q: Dr. Koltsova, can you explain how your research is focused on inflammation?

Ekaterina Koltsova, MD, PhD: We examine the role of cytokines as important mediators of inflammation and as key regulators of autoimmunity and malignancy. Because obesity is associated with chronic low-grade inflammation, it predisposes to different types of cancer, most notably liver and colon. Our work is looking at the role of the recently discovered antiinflammatory cytokine IL27 in the regulation of obesity-induced inflammation and obesity-promoted cancer.

Q: Any further comments about your research?

Rall: A consistent theme of our projects is simple: The response of one may be vastly different from that of another cell type. Cellular “tools” that differ among distinct cell populations can radically alter a cellular response to some trigger. Thus, a more sophisticated appreciation of these differences is crucial to the development of antiinflammatory modalities that might be of value in some solid tumors.
Grivennikov: We hope to pave the way for more innovative and specialized approaches to inhibit inflammatory pathways together with available therapeutic options.