Research shows that obese patients with cancers including ovarian and melanoma may respond better to a certain kind of immunotherapy than non-obese patients. Now, researchers from the University of Tennessee Health Science Center have set out to find whether this is also true for obese patients with breast cancer.
The immunotherapy drug investigated is known as a checkpoint inhibitor. Checkpoint inhibitors work by transferring substances to the body that prevent tumor cells from switching off tumour-fighting cells, and thus allow the immune system to defend itself.
In 2019 and 2020, two immune checkpoint inhibitors known as atezolizumab (an anti-PD-L1 inhibitor) and pembrolizumab (an anti-PD-1 inhibitor) were approved to treat some patients with triple-negative breast cancer, a highly aggressive form of the disease.
Obesity can cause many complexities due to its ability to both cause inflammation and activate inflammatory pathways that suppress the immune system. As such, patients with obesity tend to have worse outcomes to breast cancer treatments than non-obese patients.
For the present study, the researchers set out to find how checkpoint inhibitors could work in obese patients with breast cancer. To do so, they studied models of breast cancer in both obese and lean mice. In doing so, they found that tumors grew at a faster pace among obese mice than in their lean counterparts.
They also found that anti-PD-1 immune checkpoint blockade (ICB) was able to successfully block obesity-driven progression of cancer. ICB also increased immune cell numbers with anti-tumor immunity and effective anti-tumor markers. These results were reported both in mice both with and without obesity.
“Importantly, anti-PD-1 therapy had no impact on weight or body composition throughout the study, which rules out confounding effects of therapy-induced weight loss," write the researchers in their paper.
"This study emphasizes the complexity of examining immunotherapy in immune-competent mice with consideration of the natural variance in weight gain, tumor growth, innate regression, and response to ICB.”
While promising results, the researchers nevertheless say that future studies should match mouse models in tumor size to allow for more controlled comparisons. They also said that their study was limited as it did not examine additional outcomes including survival, recurrence after removal of therapy and metastasis, all of which are critical factors for patient care.
Sources: Medical Xpress, Cell Reports
