Medical Bulletin 27/ April/ 2024

According to a study published in the journal Nature Medicine, people with Hepatocellular Carcinoma treated with immunotherapy and a personalized anti-tumor vaccine were twice as likely to experience tumor shrinkage compared to those receiving immunotherapy only.

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and is a leading cause of cancer-related death worldwide. Despite recent advancements in systemic therapy for advanced HCC, the 5-year survival rate remains <10%. One of the newest treatment options for HCC is immunotherapy — a treatment using a person’s own immune system to fight the cancer. However, past studies show that only 15–20% of HCC diagnoses respond to immunotherapy and about 30% may be resistant.

In the study, researchers recruited 36 participants for the clinical trial. All participants received the combination of a personalized DNA vaccine, GNOS-PV02, and pembrolizumab.

At the end of the study, researchers found that almost one-third of participants experienced tumor shrinkage, which is about twice as many people seen in studies of immunotherapy alone for HCC. Additionally, about 8% of the study participants had no evidence of a tumor after receiving the combination treatment.

“The response rate on this study is high enough that I think it’s unlikely that the pembrolizumab alone did this and it supports the idea that the vaccine contributed to the efficacy observed. I think it’s also notable that the response rate was higher than pembrolizumab alone without a major increase in toxicity”

said Mark Yarchoan, lead study author.

Reference: Yarchoan, M., Gane, E.J., Marron, T.U. et al. Personalized neoantigen vaccine and pembrolizumab in advanced hepatocellular carcinoma: a phase 1/2 trial. Nat Med (2024). https://doi.org/10.1038/s41591-024-02894-y

A new study published in the journal JNCI Cancer Spectrum, published by Oxford University Press, discovered that following a healthy diet lowers the risk of cardiovascular disease in breast cancer survivors.

Cardiovascular disease is the leading cause of non-breast cancer-related mortality in women with breast cancer, who face a higher risk of cardiovascular issues compared to those without breast cancer. This increased risk is attributed to the cardiotoxic effects of breast cancer treatments and shared risk factors like aging, sedentary lifestyle, and smoking. Dietary recommendations for breast cancer survivors have been scarce, mainly relying on cancer prevention research until recent times.

In the study, researchers used data from the Pathways Study to investigate the link between diet quality and cardiovascular events in women diagnosed with invasive breast cancer. The study, comprising 3,415 participants, assessed diet quality based on the Dietary Approaches to Stop Hypertension (DASH) diet, which prioritizes fruits, vegetables, whole grains, lean protein, and low-fat dairy while limiting sodium, red meats, processed meats, and sugary beverages. Other diets, including a plant-based diet, the 2020 Healthy Eating Index, and the alternate Mediterranean diet, were also evaluated for their impact on heart health.

The results revealed that women with diets resembling the DASH diet at breast cancer diagnosis had significantly lower risks of heart failure, arrhythmia, cardiac arrest, valvular heart disease, and venous thromboembolic disease compared to those with diets less aligned with DASH. Higher intake of low-fat dairy was associated with reduced risk of cardiovascular disease-related death. Additionally, the impact of DASH on cardiovascular disease risk seemed to vary depending on the type of chemotherapy received.

“Our findings suggest that we need to begin talking to breast cancer survivors about the potential heart benefits of the DASH diet. We know that breast cancer survivors have an elevated risk for cardiovascular disease, and the diet might be able to help improve the overall health of this population”

said the paper’s lead author, Isaac J. Ergas.

Reference: Isaac J Ergas, PhD, MPH, MFA, et al,; Diet quality and cardiovascular disease risk among breast cancer survivors in the Pathways Study; JNCI Cancer Spectrum; https://doi.org/10.1093/jncics/pkae013

In a study published in the journal Nature Communications, researchers from Queen Mary University of London have found that children of women with HIV infection have an increased risk of immune abnormalities following exposure to maternal HIV viremia, immune dysfunction, and co-infections during pregnancy.

The study compared clinical outcomes between infants who were HIV-exposed and HIV-unexposed in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial. Despite high coverage of maternal antiretroviral therapy (ART) and uptake of exclusive breastfeeding, mortality in infants exposed to HIV was 41% higher than in infants not exposed to HIV. Infants who survived and remained HIV-free had impaired growth and development.

Analysis of blood samples from mothers and children in the trial revealed pathways contributing to higher infant mortality. Maternal systemic inflammation, measured by hiv,inflammation,infants,infant mortality,infections,crp,immune,pregnancyC-reactive protein (CRP), was linked to increased infant mortality, suggesting interventions targeting maternal inflammation could reduce it. HIV-exposed babies, especially boys, showed altered immune development, potentially affecting their ability to fight infections.

“Collectively, these findings show how the disrupted immune system of women with HIV in pregnancy – characterized by inflammation, immune dysfunction, and co-infections – shapes immune development in their offspring. Inflammation, as indicated by CRP, is inexpensive and simple to measure, offering the immediate opportunity for point-of-care testing to be used to identify those most at risk of infant mortality, with more support provided for high-risk pregnancies”

said Dr. Ceri Evans, NIHR Clinical Lecturer in Paediatric Infectious Diseases.

Reference: Evans, C., et al. (2024). Inflammation and cytomegalovirus viremia during pregnancy drive sex-differentiated differences in mortality and immune development in HIV-exposed infants. Nature Communications. doi.org/10.1038/s41467-023-44166-2.