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Tumor-Adjacent Dendritic Cells Crucial for Cancer Growth in T-Cell Leukemia

Jul 13, 2016 1:00:11 PM / by Steffen Porwollik

A girl with acute lymphoblastic leukemia (ALL), receiving chemotherapy. Scientists now figured out that tumor-adjacent  dendritic cells are necessary for survival and growth of primary and metastatic T-ALL – and why. Image Source: Wikimedia.Scientists examine the effect of the tumor microenvironment on cancer fate in acute lymphocytic leukemia (ALL), a disease prevalent in young children. They find that the tumor-adjacent dendritic cells provide essential cues for cancer growth.

For the past fifty years, the incidence of acute lymphocytic leukemia (ALL), a cancer of immature white blood cells, has been rising steadily. Currently, about 6,500 new cases occur annually in the US. The onset of the wretched disease is most common in early childhood, between ages 2 and 5, but can also happen later in life. Luckily, modern chemotherapy and stem cell approaches have resulted in a substantial increase in the 5-year survival rate for children affected by the disease, to over 75%. However, outlook remains poor for those that do not respond well to these therapies. As is the case for the disease’s chronic counterpart, CLL, more treatment options are sorely needed (as we recently reported).

One of three immunophenotypically distinct ALL varieties affects the T-cell progenitors (T-ALL). Scientists at the University of Texas in Austin, TX, recently focused their attention on this particular disease. In their research, they turned not to the cancer itself, but to the tissue surrounding the tumorous growth, to figure out what, if anything, was needed in that environment to facilitate tumor survival. The fascinating results of their experiments have recently been published in PNAS. [1]

In their quest, the scientists first harvested T-ALL cells from thymi of a murine cancer model. Then they cultured these cells ex vivo either alone, with wild-type thymic tissue, or with tumor-associated thymic tissue. All but the tumors co-cultured with the tumor-associated tissue died. The cancer was happily growing when co-cultured with tumor-adjacent dendritic cells - but it stopped cold in its track when the dendritic cells were removed from the culture dish. Depletion of fibroblasts or epithelial cells did not have the same effect. Apparently, the tumor-adjacent dendritic cells were needed for the tumor to survive.

But why? After extensive gene expression analysis, the scientists zoomed in on the fact that the T-ALL cells strongly expressed the receptor for insulin-like growth factor 1 (IGF1R). Moreover, T-ALL cells had a much higher percentage of phosphorylated (i.e., activated) IGF1R than normal cells - but that was only sustained when they were in co-culture with the tumor-adjacent dendritic cells. When they were grown in co-culture with wild-type dendritic cells, IGF1R did not stay activated. The scientists looked at the other side of the equation and found that those tumor-adjacent dendritic cells expressed higher levels of insulin-like growth factor 1 (IGF1) than wild-type dendritic cells, providing the necessary ingredient for activating a signal cascade that results in cancer growth. Supporting this theory, treatment of the co-cultures with IGF1R inhibitors resulted in dose-dependent reduction of primary and metastatic T-ALL growth. IGF1R signaling was therefore necessary for tumor expansion.

In conclusion, the tumor-adjacent dendritic cells were necessary for T-ALL to grow. Dendritic cells, along with many other cell populations including macrophages and CD8+ cytotoxic T-cells, are included in HemaCare’s extensive product list– do not hesitate to contact us at (877) 397-3087, if you have any questions about any of our items in the catalog. We also tailor our cell-based products according to your specific needs.

So, what’s the good news in all of this? The Texan scientists remark in a thoughtful discussion, that “… these results suggest that targeted therapies against [dendritic cells] or their tumor-promoting signals would affect tumor growth at both primary and metastatic tumor sites.” A new target in our fight against this particular cancer has been revealed. Time to forge a new weapon.

Reference

[1] Tripletta TA, Cardenasa KT, Lancastera JN, Hua Z, Seldena HJ, Jassoa GJ, et al. Endogenous dendritic cells from the tumor microenvironment support T-ALL growth via IGF1R activation. PNAS, 2016 Feb 23; 113(8):E1016-25.

Topics: leukemia, stromal cells, T Cells, T lymphocytes, Tumors, white blood cells, Basic Research

Steffen Porwollik

Written by Steffen Porwollik

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