Dr Burger Overviews the Activation, Expansion of T Follicular Helper Cells in CLL

Jan A. Burger, MD, PhD, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, highlights a study on the activation and expansion of T follicular helper cells in co-cultures of patients with CLL.

Transcript:

Hello. My name is Jan Burger. I'm a physician at MD Anderson Cancer Center in the Leukemia Department.

Oncology Learning Network: What existing data led you and your co-investigators to conduct this research?

Dr Burger: We did a study about CLL, which is a disease of lymphocytes and a subset of lymphocytes called B lymphocytes, which are immune cells, which normally produce antibodies in response to an infection or in response to vaccines.

In CLL, B lymphocytes are growing and don't stop to grow. Their growth is supported by signaling through a structure, which is called the B cell receptor.

We know for several years now that normal B lymphocytes, in order to grow, they need the B cell receptor, but they also need help from other immune cells, which are the T lymphocytes.

It's also established that T lymphocytes in CLL patients are expanded to patients who have higher numbers than usual of T lymphocytes.

Therefore, we were wondering if the normal mechanism, how T lymphocytes help the B cells to grow may also exist in CLL. Therefore, we set up conditions to study the interactions, we call it crosstalk, between CLL leukemia cells, which are B lymphocytes, and T-cells from the same patients in a culture model, which resembles in dishes what is going on in the lymph nodes of these patients.

OLN: Could you briefly describe the study and its findings?

Dr Burger: Setting up these cultures where we study CLL cells interacting with T lymphocytes, we saw that a certain subset of T lymphocytes is expanding in these cultures. These cells are called T follicular helper cells, which is a subset of T lymphocytes. Their function is to help with the growth of B lymphocytes. Something that is very similar and that is resembling the normal B cells and their requirement for this subset of T cells.

We saw that in culture dishes. We're excited about it because that's following the biology of normal B cells. Then we went also with the help of collaborators from London, we looked into lymph node sections from CLL patients to see if we can find this subset of helping T follicular helper cells, and we could find them.

What was fascinating to see in these lymph node sections from CLL patients is that these T follicular helper cells are attaching to the CLL cells, which are proliferating.

We think that is pretty strong evidence to suggest that in this leukemia and CLL, there is a mechanism that the T cells are helping the leukemia cells to grow.

Looking forward, we are thinking this should be further investigated and may lead us maybe to additional treatment options in the future.

OLN: What are the possible real-world applications of these findings in clinical practice?

Dr Burger: Obviously, in this study, which is more basic research on disease mechanism. We are not testing any specific drugs. We are starting to look into mechanism of interactions of these cells.

Potentially, if we can further advance this research, then we can dissect out certain molecules, how these T follicular helper cells are helping the leukemia cells to grow.

If we can further identify these molecules, we could potentially block them with specific reagents. Then, if that's successful, could be tested in disease models or potentially also in patients, if they are felt to be safe.

OLN: Do you and your co-investigators intend to expand upon this research? If so, what will be your next steps?

Dr Burger: If we can, we would like to go forward and do more testing. Potentially, in the models we are using of the molecules involved in these interactions between T cells and CLL cells.

Focusing on some molecules, there are some obvious ones which are, for example, chemokine receptors like CXCL5. There's CD40, CD40 ligand, which plays a role in these interactions. There are cytokines like interleukin-21. We're going to look into different areas there and see if we can see which one might be a potential target to maybe eventually benefit patients.

We have to keep in mind all these are interactions, which also play a role in normal immunity, and if we interfere with that to benefit the leukemia, we have to keep in mind it could also have an effect on normal immune responses.

That makes it a bit tricky, but I think it's definitely worth doing further research into this area.