Cancer Institute A national cancer institute
designated cancer center

Effector Lymphocytes and Molecules

Alan Krensky's work has focused on the human cytolytic T lymphocyte as an effector and regulator in the immune response. He identified the human lymphocyte function-associated antigens (LFA), identified LFA-1 deficiency state and showed that absence of cell surface LFA-1 on tumor cells (non-Hodgkin's lymphoma) was a potential mechanism of escape from immune surveillance.

He showed that IL-3 was a growth factor for human follicular lymphoma. His laboratory generated tumor immunoglobulin specific cytotoxic T lymphocytes (CTLs) that were gamma, delta TCR positive and MHC unrestricted and identified cell surface molecules involved in the CTL-tumor interaction.

Krensky also evaluated tumor specific CTL responses after idiotype vaccination for B cell (non-Hodgkin's) lymphoma, finding an association between CTL responsiveness in vitro and clinical response.

Cytolytic Molecule Granulysin

Most recently, his laboratory cloned and characterized the chemokine RANTES and cytolytic molecule granulysin, both highly relevant to tumor immunity and therapy. Granulysin has recently been described as an in vivo marker in humans for clinical outcomes in cancer and mouse models have shown that granulysin can be an effective tumor therapy.

Currently the Krensky laboratory is exploring the use of granulysin as a potential therapeutic agent in animal models of cancer. Since mice do not express granulysin, mice transgenic for human granulysin are being generated for use on animal models.

Granulysin can also be evaluated as a marker for clinical outcomes. A transcription factor (KLF13) knock out mouse shows increased expression of bcl2 with increased lymphoid cells and tissue in vivo. A chemokine lymphotactin is a marker for immune tolerance in humans. These observations are relevant to all three research goals of the Cancer Immunology Program: cell based immunotherapies, monitoring and signaling.

The KLF13 knock out mouse is an interesting model of bcl2 overexpression. Unlike published transgenic animals that have human bcl2, these knock outs express increased murine bcl2 since KLF13 is a negative regulator of bcl2 in mice. Lymphocytes and fibroblasts from these animals show a lack of apoptosis. This may prove a useful model for further evaluation of bcl2 in cancer biology.

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