A research team from Heidelberg and Dresden has found a connection between increased levels of TNF alpha in tumor tissue and an increased number of activated cytotoxic T cells that specifically recognize and kill tumors.
As such, increased levels of TNF alpha, an anti-tumor cytokine, within the tumor microenvironment can be used as an independent prognostic measure indicative of a promising disease outcome.
Usually, after colorectal cancer surgery, the extracted samples are analyzed for the presence of immune cells. When physicians discover high numbers of cytotoxic T cells, it usually correlates with a favorable disease outcome along with a decreased risk of metastasis.
Until now, researchers have not understood if the presence of T cells within the tumor microenvironment happens due to chance in less aggressive tumors, or if these cells are actually specifically programmed to become activated and respond to cancer cells, helping the body fight tumors. However, the fact that these cells are present, by itself, does not always correlate with an efficient immune response, as tumors have numerous ways of inactivating immune cells.
In this recent study, titled “Tumor-specific cytotoxic T lymphocyte activity determines colorectal cancer patient prognosis”, published in the Journal of Clinical Investigation, a research team led by Dr. Philipp Beckhove, German Cancer Research Center, collaborated with surgeons from Heidelberg and Dresden University Hospitals to assess if T cells present in colorectal tumors are actively attacking cancer cells.
The results showed that high TNF alpha levels were only present in colorectal cancer patients that also had tumor-specific memory T cells in their blood or bone marrow.
The team isolated cytotoxic T cells from 88 colorectal patient’s blood or tumor samples and found that only those activated by specific tumor proteins were able to produce TNF alpha. Moreover, the amount of TNF alpha within the tumor microenvironment significantly correlated to the number of T cells producing it.
“The TNF level in tumor tissue corresponds to the anti-cancer activity of the cytotoxic T cells,” Dr. Beckhove said in a news release. “This is strong evidence that the prognosis of colorectal cancer patients in fact depends on an active T cell response against the tumor cells. What it means is that TNF alpha levels provide a more accurate method of predicting the course of the disease, compared to simply counting the T cells in tumor tissue. If finding cytotoxic T cells that actively fight the tumor means a good prognosis, it is encouraging evidence for our attempts to develop immunotherapies based on T cells that target colorectal cancer”, he added.