Study Identifies How Some Tumors Become Resistant
Tumors that initially respond to PD- 1 and
PD-L1 immune checkpoint inhibitors often
become resistant to these treatments over
time. Using animal models of lung cancer
and melanoma, researchers found treating
tumors with checkpoint inhibitors leads to
an overproduction of CD38 proteins on CD8+ T
cells, which keeps them from killing cancer
cells. The findings could help researchers
develop anti-CD38 targeted treatments that
overcome this resistance.
LEARN MORE IN THE SEP TEMBER 2018
ASHANI WEERARATNA ON HOW OLDER
PATIENTS RESPOND TO IMMUNOTHERAPY
A Matter of Age
Your risk of being diagnosed with cancer increases as you get older. In part, that’s because your cells have had more time to collect the genetic errors that
can cause them to begin reproducing uncontrollably. Your
immune system starts working less effectively as you get
older too, making it easier for cancer cells to travel around
your body undetected.
Ashani Weeraratna, a cell and molecular biologist at the Wistar Institute
Melanoma Research Center in Philadelphia, studies the relationship between
aging and cancer. She focuses on how changes in the microenvironment—
the cells and tissue near the tumor—affect how the cancer progresses and
responds to treatment. One of Weeraratna’s recent studies, published in the
November 2018 issue of Clinical Cancer Research, found that tumors of
patients over 60 with metastatic melanoma were more likely than those of
younger patients to respond over a longer period of time to the PD- 1 inhibitor Keytruda (pembrolizumab), a type of immunotherapy. The reason: the
microenvironment around the tumors differed between younger and older
melanoma patients. Cancer Today spoke with Weeraratna about her research
and why response to cancer treatment can vary by age.
Q: How does the immune system change as we get older?
A: It’s a complex system, and there are both anti- and pro-inflammatory
changes. In older patients, the immune system is known to be less effective, which is why older people get the flu more easily and do not respond
as well [as younger people]. There also is chronic inflammation—due to an
overactive immune system—that occurs over time with aging.