IMMUNOTHERAPY

Vitamin E enhances cancer immunotherapy by reinvigorating dendritic cells via targeting checkpoint SHP1

While the popularity of dietary supplements continues, their impact on the efficacy of immunotherapy remains unknown. A recent study suggests that vitamin E can enhance immunotherapy responses through the stimulation of dendritic cell activity in the tumor (Cancer Discov 2022; doi: 10.1158/2159-8290.CD-21-0900). The researchers combined a retrospective analysis of clinical records with in-depth laboratory studies for this research. Through their analyses of electronic health records, the study authors found that survival was significantly improved among cancer patients who underwent immune checkpoint therapy and took vitamin E. Additionally, the data revealed that vitamin E enhanced responses to checkpoint inhibitors in immunogenic mouse models. However, the study authors observed that models with low levels of tumor-infiltrating dendritic cells did not benefit from vitamin E. This suggests that the effects were dependent on these cells. "Combining vitamin E with dendritic cell-recruiting cancer vaccines, or immunogenic chemotherapies, greatly boosted immune checkpoint therapy efficacy in animals," the study authors stated. "Therefore, combining vitamin E supplement, or SHP1-inhibited dendritic cells/dendritic cell-derived extracellular vesicles, with dendritic cell-enrichment therapies could substantially augment T-cell antitumor immunity and enhance the efficacies of cancer immunotherapies."

AUTHOR COMMENTARY: "This study broadens our understanding of factors that can influence responses to immunotherapies," said corresponding author Dihua Yu, MD, PhD, Chair Ad Interim of Molecular & Cellular Oncology the University of Texas MD Anderson Cancer Center. "We demonstrated that vitamin E can reinvigorate dendritic cell antigen presentation via the inhibition of SHP1. These results indicate that vitamin E-treated or SHP1-silenced dendritic cells and dendritic cell-derived extracellular vesicles could be developed as potent immunotherapies for future clinical applications."

PROSTATE CANCER

Grade migration of prostate cancer in the United States during the last decade

While changes in prostate cancer recommendations have effectively reduced overdiagnosis and overtreatment among men with low-grade disease, recent findings suggest that the incidence of higher-grade disease and metastasis at diagnosis have risen (J Natl Cancer Inst 2022; doi:10.1093/jnci/djac066). The researchers used the SEER database to identify 438,432 men with newly diagnosed prostate cancer during 2010-2018. They sought to better understand how changes in screening strategies have impacted temporal trends in Gleason grade group (GG) prostate cancer at diagnosis and radical prostatectomy pathology. Between 2010 and 2018, the data showed that the incidence of low-grade prostate cancer (GG1) decreased from 52 to 26 cases per 100, 000. The study authors reported that the incidence of GG1 as a proportion of all prostate cancer decreased from 47 percent to 32 percent. Additionally, they observed that the proportion of GG1 found on pathology in men who had a radical prostatectomy decreased from 32 percent to 10 percent. However, the research demonstrated an increase in metastases rates at diagnosis from 3.0 percent to 5.2 percent over the same period. From 2010 to 2013, the study authors reported that PSA screening rates among men (ages 50-74 years) declined from 39 to 32 per 100 men and has remained stable. There was also a modest increase in the use of magnetic resonance imaging and biomarkers, according to the researchers, from 7.2 percent in 2012 to 17 percent in 2019 and 1.3 percent in 2012 to 13 percent in 2019, respectively. "We found a significant decrease in the diagnosis and treatment of GG1 prostate cancer between 2010 and 2018. Changes in PSA screening practices appear as the primary contributor," the study authors concluded. "Public health efforts should be directed toward addressing the increase in the diagnoses of metastatic prostate cancer."

AUTHOR COMMENTARY: "To our knowledge, this is the first study to demonstrate nationally that low-grade prostate cancer is no longer the most commonly diagnosed type of prostate cancer," said senior author Jim Hu, MD, MPH, the Ronald P. Lynch Professor of Urologic Oncology at Weill Cornell Medicine and Director of the LeFrak Center for Robotic Surgery at NewYork-Presbyterian/Weill Cornell Medical Center. "One of the weaknesses of PSA/prostate cancer screening was that it led to overdetection of indolent cancers that would not harm men, subjecting them to anxiety and future testing."

THROMBOEMBOLISM

ABO blood group type and risk of venous thromboembolism in patients with cancer

Recent findings revealed that individuals with cancer and non-O blood types, such as types A, B, and AB, are at an increased risk of developing venous thromboembolism 3 months after their initial diagnosis (Blood Adv 2022; doi:10.1182/bloodadvances.2021006283). To determine the impact ABO blood type has on cancer-associated venous thromboembolism risk, the researchers collected data from 1,708 adult participants with a new or recurrent cancer diagnosis from the prospective Vienna Cancer and Thrombosis Study dataset. Of these patients, 151 developed venous thromboembolism (8.8%). The patients were grouped by blood type and then sorted based on their tumor classification. Individuals with pancreatic, gastroesophageal, and brain cancer tumors were considered to have high-risk diagnoses. The results indicated that patients with non-O blood types were more likely to develop venous thromboembolism 3 months after their diagnosis or reoccurrence of cancer, according to the study authors. They also reported an association between non-O blood type and increased venous thromboembolism risk in patients with intermediate and low thrombotic risk tumor types, but not in very high-risk types, such as pancreatic, gastroesophageal, and brain cancer. "Non-O blood type is a time-dependent predictor of venous thromboembolism in cancer patients," the study authors wrote. "It is associated with increased venous thromboembolism risk beyond 3 months of follow-up and in patients with intermediate and low-risk tumor types." These findings suggest that blood typing may serve as another important predictive measure for venous thromboembolism risk among cancer patients.

AUTHOR COMMENTARY: "Blood typing is easy to perform, can be done worldwide, and doesn't require any specialized background knowledge or equipment," said study author Cornelia Englisch, an MD-PhD student at the Medical University of Vienna. "And, of course, every risk factor that we identify helps us to understand these life-threatening complications in cancer patients better. Perhaps this will create awareness for the role blood types can play as clinical biomarkers."

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