B-Cell Non-Hodgkin's Lymphoma — Immune Response Capability Suppressed By Intratumoral T-Cells

Thursday, April 27, 2006

ROCHESTER, Minn. — Mayo Clinic researchers have shown that a subset of T-cells found in non-Hodgkin's lymphoma (NHL) patients inhibits the normal immune response to the cancer. The findings are in the May 1 issue of the journal Blood.

T-cells can be of three types: cytotoxic (Tc) — which kill infected cells; helper (TH) — which assist in several immune processes; and regulatory (Treg) — which stop the immune response when no longer necessary.

"Treg cells normally control the immune response process, ensuring that the body doesn't fight against itself," says Stephen Ansell, M.D., Ph.D., Mayo Clinic hematology researcher. "This study has shown that there is more to the story for NHL patients, and that the most common Treg cell, which is positive for the cell surface markers CD4 and CD25, actually contributes to disease progression by suppressing a healthy immune response to cancer cells."

Most NHLs consist largely of malignant B-cells, but tumors also contain T-cells that are trying to defend the body against the cancer. Several research studies have connected Treg cells with the growth of solid tumors in lung, breast, ovarian and several other cancers, and so the Mayo investigators looked at Treg cells in NHL to see if they would find a similar scenario. This is the first report that Treg cells are present in B-cell NHL and contribute to disease development.

Using tumor specimens obtained from 24 patients diagnosed with B-cell NHL, the researchers found that these Treg cells were overrepresented in B-cell NHL (17 percent) when compared to inflamed tonsil tissue (12 percent) and tumor-free lymph nodes (6 percent). They found that the Treg cells prevented the body's immune cells in the tumor from functioning appropriately. The investigators also found that not only do these Treg cells suppress the natural immune response, but they are actually 'recruited' to the tumor by the malignant B-cells. The next step is to determine whether the cancer cells actually communicate with the Treg cells and then find ways to selectively kill the Treg cells without killing the T-cells that are fighting the cancer. "This study is a step towards a greater understanding of NHL," says Zhi-Zhang Yang, M.D., the study's primary author. "We hope our continued research will eventually lead to potential treatments."

Other Mayo Clinic researchers include Anne Novak, Ph.D.; Mary Stenson and Thomas Witzig, M.D. The study was funded in part by grants from the National Institutes of Health and the Leukemia and Lymphoma Society. It results from ongoing studies conducted under the auspices of a National Cancer Institute (NCI) SPORE grant — Specialized Programs of Research Excellence, jointly held by the University of Iowa and Mayo Clinic. The Clinic currently is conducting research within six SPOREs — brain, breast, lymphoma, myeloma, pancreas and prostate cancer. For more information on SPORE projects at Mayo Clinic, visit: http://mayoresearch.mayo.edu/mayo/research/cancercenter/spore.cfm. To find out more about Mayo Clinic's hematological malignancies research, visit: http://cancercenter.mayo.edu/mayo/research/hematologic_malignancies.
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