Inflammation and Immunity in the Tumor Environment

The relationship between inflammation, innate immunity and cancer is widely accepted. Cancer-associated inflammation includes infiltrating leukocytes, cytokines, chemokines, growth factors, lipid messengers and matrix-degrading enzymes. Tumor-associated macrophages and lymphocyte subpopulations are major components of the leukocyte infiltrate in most tumors. However, the cytokine and chemokine expression profile of the tumor microenvironment may be more relevant than its specific immune cell content. Apart from inflammatory cells, tumor stroma consists of new blood vessels and connective tissue. Many factors produced by tumor cells promote tumor angiogenesis and generation of extracellular matrix. Investigations regarding the link between inflammation and cancer are vital for identifying cell or protein targets for cancer prevention and therapy. Based on the relation between inflammation and cancer, different forms of immunotherapy have been developed. In a mouse model, we investigated the potential of Streptococcus pyogenes to achieve a bacteria-related immune response against tumor cells followed by tumor regression. As a model of pancreatic carcinoma, the aggressively growing and poorly immunogenic Panc02 tumor model was chosen. Our findings showed that a local application of bacteria mediates complete tumor regression. Future investigations should focus on the optimization of immunotherapeutic approaches that incorporate live bacteria or bacterial components.

[1]  C. Starnes,et al.  Coley's toxins, tumor necrosis factor and cancer research: a historical perspective. , 1994, Pharmacology & therapeutics.

[2]  R. Weinberg,et al.  Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits , 2009, Nature Reviews Cancer.

[3]  L. Coussens,et al.  CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. , 2009, Cancer cell.

[4]  M. Karin,et al.  Immunity, Inflammation, and Cancer , 2010, Cell.

[5]  P. Allavena,et al.  Cancer-related inflammation , 2008, Nature.

[6]  K. Kinzler,et al.  Combination bacteriolytic therapy for the treatment of experimental tumors , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[7]  S. H. van der Burg,et al.  Strategies for immunotherapy of cancer. , 2000, Advances in immunology.

[8]  Shiwei Zhu,et al.  PlyC: a multimeric bacteriophage lysin. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[9]  U. Hobohm,et al.  Pathogen-associated molecular pattern in cancer immunotherapy. , 2008, Critical reviews in immunology.

[10]  P. Allavena,et al.  Cancer related inflammation: the macrophage connection. , 2008, Cancer letters.

[11]  H. Beger,et al.  Immunotherapy in pancreatic cancer – current status and future , 1999, Langenbeck's Archives of Surgery.

[12]  T. Proft,et al.  The bacterial superantigen and superantigen‐like proteins , 2008, Immunological reviews.