Monday, January 28, 2008

Kaposi’s Sarcoma and the Virus/Cancer Connection (Part 3): The Immune System Fights Cancer

In previous entries, I have discussed the connection between viruses and cancer, focusing on the roles viruses might play in the development of tumors, especially in patients with compromised immune systems. Today, I will discuss ways in which oncologists might exploit the virus/cancer connection to treat and prevent cancer.

First: Breaking News

Just to demonstrate that nothing in medicine is static for long, just this month another cancer was found to be associated with a virus. Interestingly, the discovery was made in the laboratory of the husband and wife team that identified HHV-8 as the cause of Kaposi’s sarcoma. Using a sophisticated DNA analysis technique, these scientists found that cells from a rare type of skin cancer called Merkel cell carcinoma (coincidentally, also a cancer found predominantly in the elderly) contain an embedded virus called polyoma virus. This adds Merkel cell carcinoma to the ever-expanding list of virus-associated human cancers, and increases the importance of understanding the complicated interactions between us and viruses.

polyoma virus through an electron microscope

Immune competence as cancer therapy

My discussion of viruses as a cause of cancer began with the identification of HHV-8 or KSHV as the cause of Kaposi’s sarcoma. I talked about how Kaposi’s sarcoma was an “AIDS-defining Illness” in the early days of the AIDS epidemic, and that it had virtually disappeared since the advent of highly active antiretroviral therapy (HAART), but was recently making a resurgence, at least in San Francisco. The observation that Kaposi’s sarcoma is an AIDS-defining illness that almost vanished when HIV infections became controlled with better combination treatments suggests a way to treat KS that I’ll talk about shortly.

But first… are there other virus-associated cancers that seem to depend on the patient’s immune status?

In fact, there are.

One of the most dreaded complications of organ transplantation (other than rejection) is the development of post-transplant lymphoproliferative disorder (PTLD). PTLD arises from an imbalance between lymphocytes infected with Epstein-Barr Virus (EBV) and those that keep them in check. As I discussed before, EBV is a very common virus. In the United States, estimates are that 90-95% of the adult population has had an EBV infection. Your body never rids itself of EBV. When the illness caused by the infection ends, the virus becomes dormant in white blood cells called B lymphocytes. EBV-infected B lymphocytes become immortal, and would grow without limit were it not for another type of white blood cell, called T lymphocytes, that keep the EBV-immortalized B lymphocytes under control.

Patients who have received an organ transplant must take immune suppressive drugs forever to keep from rejecting their transplant (although this may not be true… a topic for the next blog entry). When these drugs inhibit the T lymphocytes that control the EBV-infected B lymphocytes the B lymphocytes divide and grow, resulting in PTLD. PTLD can range from mild (just a swollen lymph node) to very aggressive, indistinguishable from Burkitt’s Lymphoma.

Lymph node biopsy
from a patient with
Burkitt's Lymphoma

Fortunately, the treatment for even the worst cases of PTLD begins with a very simple step – stopping the immune suppression. In many cases this is sufficient to restore the balance between the T and B lymphocytes and reverse the disease process. Ultimately, what doctors must do is find the right dose of immune suppression to prevent rejection while maintaining control over the EBV-infected lymphocytes.

Might this work for KS, too? Studies show that it might.

Patients who develop KS before they begin HAART, who are started on this treatment, have an 82.6% reduction in death from KS compared with patients who do not start HAART. In fact, HAART alone can lead to resolution of KS. Interestingly, it may be that a reduction in HIV viral load, rather than improvement in the function of the immune system, is what makes the KS go away. Regardless of why, restoring the immune system can make at least two types of virus-driven cancer (KS and PTLD) go away, with far fewer side effects than chemotherapy. Hopefully, we will continue to find ways to harness the immune system, based on this model, to fight off cancer.

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