Teizo Yoshimura, M.D., Ph.D.
Teizo  Yoshimura, M.D., Ph.D.
Staff Scientist

Dr. Yoshimura studies the mechanisms of leukocyte trafficking, especially neutrophils and monocytes, by evaluating the expression and production of chemotactic cytokines, chemokines, at sites of inflammation and cancer. He recently identified the chemokine CCL2, also known as MCP-1, as an important mediator promoting the lung metastasis of 4T1 breast cancer cells. Dr. Yoshimura recently joined Dr. Ji Ming Wang’s group and is now focused on identifying the role of the classical chemoattractant receptor, formylpeptide receptor 2, and one of its endogenous ligands, cathelin-related antimicrobial peptide (CRAMP), in inflammation-associated cancers using mouse models.

Areas of Expertise
1) inflammation, 2) chemoattractants, 3) tumor microenvironment

Contact Info

Teizo Yoshimura, M.D., Ph.D.
Center for Cancer Research
National Cancer Institute
(Office) Building 559, Room 2
Frederick, MD 21702-1201
301-846-5518
yoshimut@mail.nih.gov

Infiltration of leukocytes is a hallmark of inflammatory responses. It occurs in a number of human cancer and mouse cancer models. Although the exact role of tumor infiltrating leukocytes has not been completely understood, infiltrating leukocytes, such as tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) are generally immunosuppressive and provide a microenvironment that favors tumor growth. Therefore, identifying the mechanisms by which immunosuppressive leukocytes are recruited into tumors is critical and clinically relevant. Monocyte chemoattractant protein-1 (MCP-1)/CCL2 is a chemokine that regulates the recruitment of monocytes into sites of inflammation and cancer.

Accumulating evidence strongly suggest that the production of MCP-1 by tumors is responsible for the recruitment of immunosuppressive macrophages. In fact, recent studies demonstrated that neutralization of MCP-1 reduced the growth of prostate, breast and lung cancer in mice. Thus, MCP-1 is a molecular target of cancer treatment. The role of MCP-1 in carcinogenesis was previously studied by others. In a chemically induced skin papilloma model, the number of papilloma in MCP-1-deficient mice was lower compared to that in wild-type mice. Recently, a vital role of MCP-1 in the initiation and progression of colitis-associated colon carcinogenesis was demonstrated by using CCR2-deficient mice and MCP-1 blocking agents. However, these studies were limited to defining the role for MCP-1 in cancer induction, and the role for this chemokine in later stages of tumor development, such as tumor growth and metastasis, remains unclear.

To better define the role for MCP-1 in tumor growth and metastasis, I have generated systemic and conditional MCP-1-deficient mice. In addition, we recently generated two new mouse models which are deficient in the classical chemoattractant receptors, formyl peptide rceceptor (FPR) 1 and 2, or cathelin-related antimicrobial peptide (CRAMP), a ligand for FPR2. A better understanding of the role of chemoattractants and chemoattractant receptors in cancer development may lead us to develop a novel strategy for cancer treatment.

Selected Publications
  1. Yoshimura T, Matsushima K, Tanaka S, Robinson EA, Appella E, Oppenheim JJ, and Leonard EJ.
    Proc. Natl. Acad. Sci. U.S.A. 84: 9233-7 , 1987. [ Journal Article ]
  2. Yoshimura T, Robinson EA, Tanaka S, Appella E, Kuratsu J, Leonard EJ.
    J. Exp. Med. 169: 1449-59, 1989. [ Journal Article ]
  3. Ueda A, Ishigatsubo Y, Okubo T, Yoshimura T.
    J. Biol. Chem. 272: 31092-9, 1997. [ Journal Article ]
  4. Yoshimura T, Takahashi M.
    J. Immunol. 179: 1942-9, 2007. [ Journal Article ]
  5. Yoshimura T, Howard OM, Ito T, Kuwabara M, Matsukawa A, Chen K, Liu Y, Liu M, Oppenheim JJ, Wang JM.
    PLoS ONE. 8: e58791, 2013. [ Journal Article ]

Dr. Yoshimura obtained his M.D. degree from Kumamoto University School of Medicine, Kumamoto, Japan. He also obtained his Ph.D. in experimental pathology there, where he studied the mechanisms of macrophage infiltration into the sites of delayed-type hypersensitivity reactions with Professor Hideo Hayashi.

Research

Infiltration of leukocytes is a hallmark of inflammatory responses. It occurs in a number of human cancer and mouse cancer models. Although the exact role of tumor infiltrating leukocytes has not been completely understood, infiltrating leukocytes, such as tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) are generally immunosuppressive and provide a microenvironment that favors tumor growth. Therefore, identifying the mechanisms by which immunosuppressive leukocytes are recruited into tumors is critical and clinically relevant. Monocyte chemoattractant protein-1 (MCP-1)/CCL2 is a chemokine that regulates the recruitment of monocytes into sites of inflammation and cancer.

Accumulating evidence strongly suggest that the production of MCP-1 by tumors is responsible for the recruitment of immunosuppressive macrophages. In fact, recent studies demonstrated that neutralization of MCP-1 reduced the growth of prostate, breast and lung cancer in mice. Thus, MCP-1 is a molecular target of cancer treatment. The role of MCP-1 in carcinogenesis was previously studied by others. In a chemically induced skin papilloma model, the number of papilloma in MCP-1-deficient mice was lower compared to that in wild-type mice. Recently, a vital role of MCP-1 in the initiation and progression of colitis-associated colon carcinogenesis was demonstrated by using CCR2-deficient mice and MCP-1 blocking agents. However, these studies were limited to defining the role for MCP-1 in cancer induction, and the role for this chemokine in later stages of tumor development, such as tumor growth and metastasis, remains unclear.

To better define the role for MCP-1 in tumor growth and metastasis, I have generated systemic and conditional MCP-1-deficient mice. In addition, we recently generated two new mouse models which are deficient in the classical chemoattractant receptors, formyl peptide rceceptor (FPR) 1 and 2, or cathelin-related antimicrobial peptide (CRAMP), a ligand for FPR2. A better understanding of the role of chemoattractants and chemoattractant receptors in cancer development may lead us to develop a novel strategy for cancer treatment.

Publications

Selected Publications
  1. Yoshimura T, Matsushima K, Tanaka S, Robinson EA, Appella E, Oppenheim JJ, and Leonard EJ.
    Proc. Natl. Acad. Sci. U.S.A. 84: 9233-7 , 1987. [ Journal Article ]
  2. Yoshimura T, Robinson EA, Tanaka S, Appella E, Kuratsu J, Leonard EJ.
    J. Exp. Med. 169: 1449-59, 1989. [ Journal Article ]
  3. Ueda A, Ishigatsubo Y, Okubo T, Yoshimura T.
    J. Biol. Chem. 272: 31092-9, 1997. [ Journal Article ]
  4. Yoshimura T, Takahashi M.
    J. Immunol. 179: 1942-9, 2007. [ Journal Article ]
  5. Yoshimura T, Howard OM, Ito T, Kuwabara M, Matsukawa A, Chen K, Liu Y, Liu M, Oppenheim JJ, Wang JM.
    PLoS ONE. 8: e58791, 2013. [ Journal Article ]

Biography

Dr. Yoshimura obtained his M.D. degree from Kumamoto University School of Medicine, Kumamoto, Japan. He also obtained his Ph.D. in experimental pathology there, where he studied the mechanisms of macrophage infiltration into the sites of delayed-type hypersensitivity reactions with Professor Hideo Hayashi.