TWiV 1159: Eliminating Cervical Cancer, and Endometrial Immunity
0:00 Introduction: Vincent Racaniello introduces the episode, recorded at the Karolinska Institute in Stockholm, featuring Niklas Björkström and Joakim Dillner.
0:28 Guests' Backgrounds: Björkström discusses his background in engineering, switching to medicine due to an interest in immunology, and his current research focus on clinical microbiology. Dillner shares his journey into tumor biology, his research on Epstein-Barr virus and papillomaviruses, and his current role in infectious disease epidemiology and cervical cancer elimination.
7:01 Studying Endometrial Immune System: Björkström explains the rationale for studying the immune cell population in the endometrium, highlighting its role in pregnancy tolerance, defense against infections, and its dynamic regeneration during the menstrual cycle.
11:16 Monozygotic Twin Study: The study uses monozygotic twins to eliminate genetic variability and focus on non-heritable influences on the endometrial immune system. It also includes a cohort of non-twins to assess stability and randomness in immune system composition.
16:19 Menstrual Blood as a Sample Source: Menstrual blood is used as a minimally invasive way to sample the endometrial microenvironment, particularly during the first two days of menstruation when it contains a high proportion of endometrial cells.
19:11 Data Analysis: The study employs flow cytometry, proteomics, transcriptomics, and epigenetic analysis to investigate the endometrial immune system.
19:18 Study Findings: The study reveals that the endometrial immune system exhibits greater variability compared to peripheral blood, and that different environmental factors drive immune diversity in the endometrium compared to circulation.
22:24 Key Immune Cell Differences: Significant differences in mucosal natural killer (uNK) cells and CD8+ tissue-resident memory (TRM) cells are observed between the endometrium and peripheral blood.
24:29 Endometrial Tolerogenicity: The uterus appears to have a more tolerogenic immune environment, likely influenced by factors like TGF-beta, which is crucial for pregnancy but also presents a balance challenge to prevent infections.
25:34 Assessing Heritability: The study uses twin data and longitudinal sampling to assess heritable versus non-heritable immune responses, focusing on factors like CMV infection, menstrual cycle stage, pregnancy history, and hormonal contraceptive use.
27:06 CMV's Impact on Immune Systems: CMV is identified as a major driver of immune diversity in peripheral blood but shows minimal impact on the uterine immune system, despite the presence of CMV-specific CD8+ T cells in the uterus.
29:11 Hormonal Influence: Sexual hormones, particularly progesterone, are found to have a major impact on the local immune system in the endometrium, influencing the differentiation of immune cells, while not significantly affecting circulating cells.
33:28 Pregnancy's Effects: The study discusses the limitations in assessing pregnancy's long-term effects on the endometrial immune system due to the need for longitudinal studies. Future research aims to investigate pregnancy-induced changes and the concept of “memory of pregnancy.”
34:34 Preeclampsia Research: The study touches upon the potential of this research framework to better understand conditions like preeclampsia, a pregnancy disorder related to the inadequate development of spiral arteries in the endometrium.
40:01 HPV and Cervical Cancer: Joakim Dillner discusses HPV, the global burden of cervical cancer, the role of screening in prevention, and the effectiveness of HPV vaccines in targeting the most oncogenic types.
44:02 Oncogenic vs. Benign HPV Types: The discussion explores the mechanisms by which certain HPV types are oncogenic, focusing on the E6 and E7 proteins' ability to antagonize tumor suppressor proteins like p53 and RB, leading to uncontrolled cell division.
52:16 HPV Vaccines and Elimination Strategies: The episode covers the current status of HPV vaccination in Sweden, its impact on cervical cancer rates, the ongoing efforts to eliminate cervical cancer by 2027, and the challenges in reaching herd immunity.
56:50 HPV Persistence and Immune Factors: The discussion delves into the factors contributing to persistent HPV infection in a subset of individuals, highlighting the role of immunological factors like HLA associations.
1:06:47 Covid-19 Pandemic's Impact: The impact of the COVID-19 pandemic on HPV vaccination and screening is discussed, noting minimal disruption to vaccination in Sweden but a shift towards home-based sampling for screening, which has increased participation rates.
1:12:59 HPV Screening with PCR: Sweden's transition from pap smears to HPV-based screening using PCR is highlighted, emphasizing the effectiveness of this approach in detecting high-risk HPV infections and guiding treatment decisions.
1:15:39 Cervical Cancer Elimination in Sweden: The episode concludes with a discussion of Sweden's goal to eliminate cervical cancer by 2027, the strategies employed to achieve this, and the comparison with other countries' efforts in cervical cancer elimination.