Swollen Lymph Nodes in Groin: Causes, Diagnosis, and Treatments
The Immune-modulatory Effect Of Lenvatinib Investigated In New Study
New drugs are being developed and used to combat a variety of malignancies. Among these is lenvatinib, an antagonist of multiple growth factors, including vascular endothelial growth factor receptor (VEGFR) 1-3, fibroblast growth factor receptor (FGFR) 1-4, and platelet derived growth factor receptor alpha, which allows this agent to inhibit angiogenesis and cell proliferation.
Lenvatinib is currently used to treat differentiated thyroid carcinoma (DTC) which is refractory to radioactive iodine (RAI). A new study published in Scientific Reports explores the effect of lenvatinib treatment on patients with advanced thyroid cancer.
Study: Changes in peripheral blood immune cell population in thyroid cancer patients treated with lenvatinib. Image Credit: crystal light / Shutterstock.Com
IntroductionLenvatinib is associated with superior real-world efficacy against RAI-refractory DTC, perhaps because it blocks both FGFR and VEGFR. This prevents the emergence of resistance to this agent, thereby prolonging its duration of efficacy.
Lenvatinib also has a possible immunomodulatory effect, which is currently being evaluated in preclinical studies. These immunomodulatory effects include better tumor infiltration, natural killer (NK) cell activation, and reduced tumor-associated macrophages. NK cells are central to the innate immune antitumor response, as they mediate the natural cytotoxic reaction to tumor cells, thereby inhibiting their growth and spread.
The current study sought to confirm this activity of lenvatinib using peripheral blood mononuclear cell (PBMC) profiles as a marker of host immunity in lieu of tumor-infiltrating immune cell measurements. To this end, the peripheral immune cell profile was compared between two and four times for each patient at two to three month intervals using the Maxpar Direct Immune Profiling Assay.
A total of ten patients were included in the current study, with a mean of three samples obtained from each patient. The median age of the patients was 65 years.
What did the study show?All patients responded well to lenvatinib, which showed a durable effect. The major difference between the PBMC profiles when pre-treatment, on-treatment, and off-treatment samples were compared was the proportion of NK cells.
Among total live PBMCs, NK cells accounted for 9% before treatment and subsequently rose to about 21% in on-treatment samples, the latter of which comprised both early and late NK cells. In off-treatment samples, NK cell levels declined to 13%, with a significant reduction in early NK cells in this group.
Following treatment, the total NK cell proportion also rose significantly in the CD45 cell subgroup from about 10% to 19%. There were no significant changes in monocyte proportions or the lymphocyte-to-monocyte ratio (LMR).
The assessed cytokines included interleukin 2 (IL-2) and IL-15 among the NK cell activators, as well as IL-10 and transforming growth factor β (TGFβ) among NK cell inhibitors, all of which did not change significantly following treatment.
What are the implications?Our results present the immune-modulatory effect of lenvatinib in a real-world clinical setting."
Taken together, the study findings demonstrate that NK cell populations significantly increased in thyroid cancer patients treated with lenvatinib.
These findings corroborate earlier research conducted in hepatocellular carcinoma mouse models, in which immunocompetent mice responded to lenvatinib better than immunocompromised mice. Other studies also suggested that lenvatinib has immunomodulatory capabilities, as treatment with this agent allowed immune cells to infiltrate the tumor better and activate NK cells.
Lenvatinib and sorafenib belong to the same drug category; however, the superior performance of lenvatinib in preclinical trials may be attributed to its ability to improve the immune antitumor response. Additional studies are needed to validate these findings using a large group of patients.
Changes in the neutrophil-lymphocyte ratio (NLR) and polymorphonuclear myeloid derived suppressor cells (PMN-MDSCs) have been reported in earlier research. These observations also necessitate additional research, as they were not measured in the current study.
While previous reports suggest that tumor cells express higher levels of chemokines and that NK cells exhibit an increased expression of adhesion molecules in mice treated with lenvatinib, the current study did not identify significant changes in cytokines associated with NK cell activity. Larger studies with more cytokine assays may elucidate this association.
NK cells are part of the innate immune response and destroy tumor cells by blocking their proliferation, growth, and migration. Considering the risk of immune evasion in some cancers, chimeric antigen receptor (CAR)-modified NK cells have been used to enable NK cells to perform their cytotoxic function in such tumors.
Considering the effect of lenvatinib on NK cells, sequence or combination therapies of lenvatinib with CAR-NK cell therapy are expected to show synergy in patients with thyroid cancer."
Common Signs Of An Overactive Thyroid That Could Be Missed During Hot Weather
Warm skin and excessive sweating could be a sign of hyperthyroidism (Image: Getty Images)With the temperature changes that come with summer many of us will notice changes to our bodies.
For some the heat is welcome, while for others it can lead to difficulty getting to sleep at night and sweating more than usual.
Although these side effects of the warmth are generally nothing to worry about, they could be masking something more serious.
According to the NHS, there are two symptoms of an overactive thyroid that could be mistaken for the effects of hot weather.
Also known as hyperthyroidism, having an overactive thyroid means the thyroid gland is producing too much of the thyroid hormones.
Weight loss is one sign of hyperthyroidism (Image: Getty)The thyroid is a small gland in the neck located just in front of the windpipe.
Thyroid hormones control your metabolism - the process of converting food into energy.
Having too much or too little (hypothyroidism) of thyroid hormones can therefore have a significant impact on your body.
The NHS warns that people with hyperthyroidism might experience warm skin and excessive sweating - also both side effects of heat.
"An overactive thyroid (hyperthyroidism) can cause a wide range of symptoms, although it's unlikely you'll experience all of them," the NHS explains.
"The symptoms may develop gradually or suddenly. For some people they're mild, but for others they can be severe and significantly affect their life."
It lists other common signs of hyperthyroidism as:
Other physical signs to look for include:
If you experience any signs of hyperthyroidism you should speak to your doctor.
Treatment options for the condition include medicine, radioactive iodine treatment and surgery.
"It might be useful to make a list of all your symptoms and show it to a GP," the NHS adds.
"These symptoms and signs can have a number of causes. But a blood test can often help to determine whether they're caused by a thyroid problem."
HypothyroidismIf your thyroid gland does not produce enough of the thyroid hormones you could have an underactive thyroid - hypothyroidism.
Common symptoms of this are tiredness, weight gain and depression.
However it can also cause:
Comments
Post a Comment