Immune Cell Delivers ‘Kiss of Death’ to Cancer
The immune system plays a major role in cancer, from seeking out and destroying cancer cells when they first form, to eventually being overcome and even co-opted to ignore or protect the tumor mass. Clinicians and researchers have been investigating how best to boost and re-activate the immune system’s natural ability to attack cancer. Now a team at Jefferson led by the laboratories of Yuri Sykulev, M.D., Ph.D., from the Department of Microbiology and Immunology and Takami Sato, M.D.,Ph.D., from Medical Oncology have discovered how immune cells deliver a “kiss of death” to cancer.
There are many types of immune cells that can play a role in killing cancer cells. The advantage of the type of cells Sykulev studies, natural killer cells, is that they grab the cancer cell with many arms like an octopus, hold on tightly while they quickly deliver a large payload of toxins, called cytolytic granules, to the cancer cell – the kiss of death – work that Dr. Sykulev helped demonstrate. Other immune cells may attach with one or two arms, and therefore may not be able to hold on strongly enough to send a strong and rapid death signal.
Drs. Sykulev and Sato have now added a searchlight function to these NK cells, by attaching an antibody molecule that seeks out the cancer – specifically liver metastases – to help them deliver the deadly payload with more precision.
Surprisingly High Rates of Depression in Asian Americans
A study by Jefferson’s Hee-Soon Juon, Ph.D., a Professor of Medical Oncology that pooled data from 58 previous studies to analyze a population of 21,731 Asian Americans showed that rates of depression in Asian Americans are higher than the general American population. The results suggest that there may be a need for interventions that target this population with culturally sensitive messaging, says Dr. Juon.
Depression tends to manifest differently in Asian American adults than it does in the European American communities, and can be missed by health practitioners. “There are many language barriers for Asian Americans,” says Dr. Juon. In addition, “Asian Americans who are depressed tend to complain about physical symptoms like joint pain, rather using words like ‘sadness’ or ‘depression’. Also, it can be extremely challenging to find a practicing psychologist who speaks the native language of the patient, requiring a translator, which adds to the barriers for treatment.”
In addition, the size of the study allowed the researchers to look at the Asian American community not as a homogenous pool, but rather to tease out the rates of depression across different countries of origin. Dr. Juon’s team found, for example, that the prevalence of depression for Koreans and Filipinos was 33 and 34 percent, respectively, whereas for Chinese it was significantly lower, at 16 percent.
“Depression is stigmatized in many cultures. In Asian American communities it is very stigmatized,” says Dr. Juon, whose work includes creating educational materials on health topics that are important to Asian American communities.
Racial Disparities in Heart Disease: A Close Look at Clotting
Black Americans are more likely to have heart disease and more likely to die from the disease. While disparities in healthcare access and bias certainly play a role, new research from Paul Bray, M.D., Director of the Cardeza Foundation of Hematologic Research at Jefferson suggest that differences in genetic make-up may also play a role.
One of Dr. Bray and colleagues’ key discoveries is that the platelets — a cell circulating in the blood stream that causes clots in heart vessels – of Black Americans are “hyper-sensitive” to thrombin, a blood clotting agent. This racial difference is caused by a slight variation in the genetic code of the platelet protein called PAR4, making platelets from blacks “stickier” than platelets from whites. Further studies from Dr. Bray’s laboratory suggest that heart disease in black patients might not be held in check by most of the currently FDA-approved heart medications that work by blocking blood clots (known as blood thinners). Notably, although the newly identified PAR4 risk variant is most common in blacks, it is also present in smaller percentages of individuals of non-African ancestry.
With the government R01 grant recently received by Dr. Bray’s lab, the researchers plan to bore further down into how the PAR4 gene variant resists common blood thinners and also screen large databases of patient data to determine if having the PAR4 variant predisposes patients to heart disease or to worse outcomes despite current best care. The group is screening drug libraries to identify better drugs to treat patients with PAR4 risk variant, and will also work to understand how to use and dose currently approved medications so that they are more effective at treating patients with the PAR4 gene variant.