Emerging research unveiled at the European Congress on Obesity (ECO) 2026 in Istanbul marks a significant advance in understanding how adult weight gain influences cancer risk over the life course. Conducted by Associate Professors Anton Nilsson and Tanja Stocks at Lund University’s Department of Translational Medicine, the expansive study assesses longitudinal weight trajectories from late adolescence through middle age, revealing stark correlations between progressive weight increases and heightened incidence of multiple cancers.

Obesity’s pervasive role as a global health challenge is well documented, currently affecting approximately one in eight individuals worldwide. Beyond its known metabolic consequences, obesity is increasingly recognized as a major oncogenic driver. The International Agency for Research on Cancer (IARC) has robustly linked excess adiposity with increased risks of cancers of the oesophagus (particularly adenocarcinoma), gastric cardia, colorectal region, liver, gallbladder, pancreas, postmenopausal breast, endometrium, ovaries, kidneys, meninges, thyroid gland, and hematologic malignancies such as multiple myeloma. However, many prior studies have examined obesity and cancer risk based on a snapshot of body weight at a single adult life stage, often neglecting the dynamic nature of weight changes across decades.

This latest investigation addresses this critical gap by leveraging the ODDS study—an extensive pooled, nationwide Swedish cohort—encompassing weight data from 1911 to 2020 combined with cancer registries extending through 2023. The dataset includes over 630,000 participants (251,041 men and 378,981 women), each with an average of four weight measurements taken between ages 17 and 60. By modeling individual weight trajectories over this 43-year span, the study elucidates nuanced associations between temporal weight gain patterns and site-specific cancer risk, shedding light on how the biology of adiposity’s oncogenic influence might vary by sex, cancer type, and timing of weight gain.

The data compellingly demonstrate that individuals in the highest quintile of adult weight gain face significantly elevated risks of developing several established obesity-related cancers, with men experiencing a 7% greater risk of any cancer and women a striking 17% increase compared to the lowest quintile. More dramatically, risks for firmly established obesity-related cancers spike by 46% in men and 43% in women within the highest weight gain category. Specific malignancies manifesting the most potent associations included liver and oesophageal adenocarcinoma in men, with hazard ratios of 2.67 and 2.25 respectively, and endometrial cancer in women with a hazard ratio of 3.78—indicating nearly quadruple the risk in the highest weight gain group.

Beyond these headline findings, moderate but statistically significant elevations in risk surfaced for gastric cardia and rectal cancers in men, postmenopausal breast cancer and meningioma in women, and colorectal and renal cell carcinomas in both sexes. Intriguingly, the study also identified cancers not previously classified as obesity-related but now showing meaningful associations with weight gain, such as pituitary tumors exhibiting more than a twofold increased risk in both sexes among high gainers, as well as men’s increased occurrences of malignant melanoma and diffuse large B-cell lymphoma, and women’s parathyroid gland tumors.

Another pivotal insight emerges from examining weight at age 17 before adulthood commenced. Here, the highest 20% cohort by weight similarly exhibited elevated cancer risks, often paralleling those attributable to adult weight gain. This suggests that both baseline adiposity entering adulthood and subsequent weight increases synergistically contribute to the lifetime cancer burden, challenging the emphasis on midlife body mass alone as a critical window for intervention.

The timing of weight gain throughout adulthood reveals additional complexity. The authors segmented adult life into early, middle, and later periods, discovering sex-specific and cancer-site specific patterns. For men, early and middle adulthood weight gain showed stronger associations with obesity-related cancers, especially for liver and oesophageal cancers. Conversely, for women, weight gain in middle to later adulthood periods was more strongly linked to endometrial, postmenopausal breast, and meningioma risks. When excluding female-specific cancers, women’s associations with weight gain were uniformly distributed across all age intervals, hinting at hormonal influences shaping these disparities.

Cancer etiologies appeared to interact differentially with the timing of adiposity increases. Renal cell carcinoma among men correlated most with early weight surge, liver and colon cancers aligned closely with middle adulthood changes in both sexes, and gastric cardia cancer alongside meningioma showed stronger trends with later adulthood weight gains. However, most of these distinctions did not reach strict statistical significance, underscoring the need for larger samples or alternative modeling approaches to fully elucidate these temporal nuances.

The analysis extended to age of obesity onset, revealing cancer incidence progressively increased the earlier obesity developed. Notably, men becoming obese before 30 years of age faced fivefold liver cancer risk, doubled pancreatic and renal cell cancer incidence, and a 58% increased colon cancer susceptibility. Women with early onset obesity experienced a 4.5-fold endometrial cancer risk, substantially heightened pancreatic and meningioma risks, and a doubled renal cell carcinoma risk compared to never-obese counterparts. These findings underscore the cumulative carcinogenic burden of prolonged excess adiposity, amplifying calls for early preventive interventions.

Mechanistically, the study’s results align with growing evidence that obesity-driven cancer pathogenesis is multifactorial. Key pathways implicated include dysregulated sex hormone metabolism, aberrant insulin signalling cascades, adipokine imbalances, and heightened systemic inflammation—each exerting tissue-specific oncogenic effects. In men, chronic inflammation and insulin resistance, compounded by gastroesophageal reflux disease in oesophageal adenocarcinoma, may explain the strong associations seen. For women, hormone-sensitive tumors involving endometrium and breast tissue reflect the pivotal role of excess adiposity in estrogen metabolism and receptor activation. Additionally, novel associations with pituitary tumors invite further exploration into neuroendocrine mechanisms modulated by obesity.

The investigators conclude that a life-course perspective on weight management is paramount in cancer prevention strategies. Their comprehensive longitudinal analysis emphasizes that both early adult body weight and subsequent weight gain exert substantial influences on risks across a spectrum of established and emerging obesity-related cancers. Given the ongoing global rise in obesity prevalence and its intersection with increasing cancer incidence, the findings provide compelling impetus to implement timely, sex-aware, and sustained weight control measures throughout adulthood.

This research represents a paradigm shift toward integrating temporal weight trajectories into oncologic risk assessment and public health policies. It lays the groundwork for future mechanistic studies and clinical trials aimed at disentangling the complex interplay of adiposity and carcinogenesis, ultimately elevating precision prevention in oncology.

For further information, the full preprint is available at medRxiv, and the authors welcome inquiries regarding this transformative work.

Subject of Research:
Longitudinal impact of adult weight gain on incidence of established and potential obesity-related cancers.

Article Title:
Not specified in the provided content.

News Publication Date:
May 2026 (in conjunction with ECO 2026, 12-15 May).

Web References:
https://www.medrxiv.org/content/10.64898/2026.04.23.26351553v1

References:
Not explicitly provided in the text.

Image Credits:
Not mentioned.

Keywords:
Obesity, Cancer risk, Weight gain trajectory, Longitudinal cohort, Epidemiology, Life-course analysis, Liver cancer, Endometrial cancer, Esophageal adenocarcinoma, Renal cell carcinoma, Pituitary tumors, Sex differences, Obesity-related cancers.

Dendritic cells serve as the immune system’s sentinels, orchestrating the detection and elimination of threats such as pathogens and tumor cells. They function as antigen-presenting cells that educate and activate other immune components, particularly T cells, to initiate targeted immune responses. The diversity within dendritic cell populations allows the immune system to tailor its approach, responding effectively to the exact nature of the challenge it encounters. However, the genetic and molecular mechanisms that underlie this cellular heterogeneity have long remained elusive.

Addressing this knowledge gap, the Lund University research team embarked on an ambitious project to systematically decode the transcriptional regulation processes that dictate dendritic cell development from precursor cells. By screening a comprehensive library of seventy different transcription factors—proteins responsible for selectively activating or repressing genes—they identified two unique combinations capable of reprogramming skin or cancer cells into distinct dendritic cell subsets: conventional type 2 dendritic cells (cDC2) and plasmacytoid dendritic cells (pDC).

The power of this approach lies in its nuanced understanding of the epigenetic landscape. Early in the reprogramming process, these transcription factors modify chromatin accessibility, effectively “unlocking” different regions of the genome associated with dendritic cell identity. This orchestrated genomic remodeling steers the fate of transformed cells, enabling them to acquire specialized functions characteristic of their destined dendritic cell subtype.

Filipe Pereira, professor of molecular medicine and lead investigator on the project, describes the discovery as analogous to revealing the immune system’s construction manual. “By identifying the precise sets of transcription factors that build these dendritic cell types, we enable the potential to manufacture tailored immune cells that can more effectively direct the body’s defenses against cancer,” Pereira explains. This insight offers a strategic advantage in immunotherapy, where generating patient-specific immune cells capable of recognizing and attacking tumours remains a central challenge.

To validate their findings, the team deployed mouse models of cancer, utilizing engineered dendritic cells derived through their reprogramming protocol. Remarkably, these cells elicited robust immune responses against melanoma and breast cancer, mirroring the activity of naturally occurring dendritic cells but with enhanced targeting capabilities. This suggests a promising therapeutic avenue where such engineered dendritic cells could be administered to patients, augmenting the immune system’s precision and potency in combatting malignancies.

Moreover, the implications of this research extend beyond cancer. Dendritic cells are also pivotal in autoimmune conditions, where inappropriate immune activation damages healthy tissue. Certain dendritic cell subtypes play immunosuppressive roles, maintaining balance and preventing excessive inflammation. The ability to program cells into these anti-inflammatory dendritic phenotypes could pave the way for novel treatments in conditions like rheumatoid arthritis or multiple sclerosis, where immune modulation remains a therapeutic priority.

This study represents the first systematic blueprint of transcriptional circuits governing dendritic cell heterogeneity, transcending previous efforts that identified individual factors without appreciating their combinatorial complexity. The methodology involved high-throughput screenings, capturing multifactorial interactions that more accurately reflect the in vivo environment, thus enhancing the translational relevance of the findings.

As cancer immunotherapy continues to evolve, one of its persistent limitations is the variability in patient response rates. Many patients exhibit resistance or relapse despite advances with checkpoint inhibitors or CAR-T therapies. Tailoring immunotherapies at the cellular level, by introducing highly specific dendritic cell subtypes capable of directing more precise immune responses, could address this disparity, ushering in an era of personalized oncology treatment.

The research also underscores the importance of epigenetic regulation in immune cell differentiation. By understanding how transcription factors modify chromatin landscapes to establish dendritic cell identity, future therapies might leverage epigenetic modulators, refining immune interventions without necessitating extensive genetic engineering.

Furthermore, this discovery invites a reevaluation of the developmental pathways of immune cells. The capacity to reprogram somatic cells into functional immune cell subsets challenges traditional notions of cellular plasticity, opening avenues for regenerative immunology and vaccine development. Custom-designed dendritic cells could enhance vaccine efficacy by presenting antigens with greater efficiency and specificity.

While the translational application of these findings is still emerging, with necessary validation in human systems and clinical trials ahead, the groundwork laid by Professor Pereira’s team charts a clear path forward. Their work is a testament to the power of integrative molecular biology and bioinformatics, exemplifying how targeted screening strategies can unlock biological complexity and inform therapeutic innovation.

In conclusion, the identification of transcription factor blueprints that govern dendritic cell subset identity extends the frontiers of cancer immunotherapy and immunology at large. By harnessing the molecular tools to generate bespoke immune cells, this research not only offers hope for more effective, individualized cancer treatments but also heralds transformative possibilities for managing autoimmune diseases and enhancing immune system modulation across a spectrum of health challenges.

Subject of Research: Animals

Article Title: Anchored screening identifies transcription factor blueprints underlying dendritic cell diversity and subset-specific anti-tumor immunity

News Publication Date: 29-Aug-2025

Web References: https://dx.doi.org/10.1016/j.immuni.2025.08.001

Image Credits: Kennet Ruona

Keywords: dendritic cells, transcription factors, cellular reprogramming, cancer immunotherapy, immune system, epigenetics, immune cell plasticity, personalized medicine, melanoma, breast cancer, immunosuppression, autoimmune diseases

Neuroblastoma predominantly affects infants and young children and is notorious for its aggressive behavior and poor prognosis, especially in cases where the disease has metastasized. Conventional treatment regimens encompass an aggressive combination of surgery, chemotherapy, radiation, and immunotherapy. While these modalities have benefited some patients, those with metastatic disease frequently encounter treatment resistance and relapse. Moreover, survivors of neuroblastoma often endure severe long-term cognitive deficits due to the toxicity of current therapies, underscoring the urgent necessity for more targeted, less harmful interventions.

Differentiation therapy has emerged as an appealing conceptual framework in the fight against neuroblastoma. The therapeutic goal is to induce malignant cells to exit their proliferative, undifferentiated state and instead mature into non-proliferative, functionally specialized cells. Retinoic acid, a derivative of vitamin A, has been the mainstay differentiation agent used clinically; however, its effectiveness is limited by variable patient response rates and the common development of resistance during treatment. This clinical challenge has galvanized efforts to identify alternative molecular targets capable of steering neuroblastoma cells toward benign differentiation.

The Swedish research team turned their attention to two antioxidant enzymes, PRDX6 (Peroxiredoxin 6) and GSTP1 (Glutathione S-transferase Pi 1), both of which play pivotal roles in cellular redox homeostasis within cancer cells. Neuroblastoma cells are characterized by elevated oxidative stress due to their high metabolic activity, leading to an increased dependence on antioxidant systems to neutralize reactive oxygen species (ROS) and prevent apoptotic cell death. Elevated expression of PRDX6 and GSTP1 correlates with more aggressive disease and worse patient outcomes, suggesting that these enzymes are instrumental in cancer cell survival and proliferation.

Through meticulous in vitro experiments and rigorous in vivo studies using mouse models, the researchers demonstrated that dual inhibition of PRDX6 and GSTP1 not only induces selective death in a subset of neuroblastoma cells but also prompts a considerable fraction of surviving cells to differentiate into mature neurons. This phenotypic conversion effectively stymies tumor expansion by depleting the pool of undifferentiated, malignant cells. Importantly, the differentiated neurons exhibited functional characteristics akin to healthy nerve cells, indicating a functional reprogramming rather than mere phenotypic mimicry.

The mechanistic underpinnings of this differentiation induction appear to hinge on disrupting the antioxidant defenses that cancer cells exploit to maintain their malignant state. By pharmacologically inhibiting PRDX6 and GSTP1, the elevated oxidative stress surpasses a critical threshold, leading to selective vulnerability of cancer cells. Unlike traditional cytotoxic strategies that indiscriminately target dividing cells, this approach leverages the cancer cells’ own metabolic fragility to facilitate a therapeutic conversion, thereby potentially minimizing collateral damage to healthy tissues.

A particularly exciting aspect of this study is the translational potential of one of the enzyme inhibitors, which has already been granted orphan drug designation by the US Food and Drug Administration for a separate adult indication. This regulatory recognition not only underscores the compound’s safety profile but also accelerates its candidacy for clinical trials in pediatric neuroblastoma. The planned transition from preclinical models to human studies represents a critical next phase to evaluate safety, dosing parameters, and efficacy in the vulnerable pediatric population.

The repercussions of this research extend beyond neuroblastoma treatment. By exemplifying how targeting metabolic and redox vulnerabilities can induce differentiation in malignant cells, the study paves the way for broader applications in other cancers exhibiting similar dependencies. Furthermore, this enzymatic dual inhibition strategy might be combined synergistically with existing therapies, such as immunotherapy or low-dose chemotherapy, to enhance overall treatment outcomes while reducing long-term adverse effects.

Notwithstanding these promising findings, several challenges remain before clinical implementation can be realized. The complexity of neuroblastoma heterogeneity necessitates further studies to identify biomarkers that predict patient responsiveness to PRDX6 and GSTP1 inhibitors. Additionally, long-term effects of differentiated neurons within the tumor microenvironment need rigorous examination to ensure they do not revert to malignancy or adversely affect surrounding neural tissue. Comprehensive safety assessments are crucial given the delicate nature of pediatric neural systems.

Funding for this pivotal research was primarily provided by prominent Swedish organizations — the Swedish Research Council, the Swedish Cancer Society, the Swedish Childhood Cancer Fund, and the Radiumhemmet Research Funds — underscoring the national commitment to addressing childhood cancer. The researchers have also explicitly disclosed no conflicts of interest, enhancing the credibility and impartiality of the findings.

In summary, the innovative strategy of combining PRDX6 and GSTP1 inhibition to coerce neuroblastoma cells into differentiation marks a paradigm shift in pediatric oncology. By transforming malignant cells into harmless neurons, this approach may radically alter the therapeutic landscape, offering hope for improved survival rates and quality of life among afflicted children. As the scientific community eagerly anticipates forthcoming clinical trials, this study stands as a compelling testament to the power of molecular precision medicine in combating childhood cancers.

Subject of Research: Animals

Article Title: Combined targeting of PRDX6 and GSTP1 as a potential differentiation strategy for neuroblastoma treatment

News Publication Date: 16 June 2025

Web References:
DOI link – 10.1073/pnas.2427211122

References:
Judit Liaño-Pons, Elisa Garde-Lapido, Fenja L. Fahrig, Merle Jäckering, Ye Yuan, Stina Andersson, Lea Schort, Maria Esteve, Sofie Mohlin, Oscar C. Bedoya-Reina, Marie Arsenian-Henriksson, “Combined targeting of PRDX6 and GSTP1 as a potential differentiation strategy for neuroblastoma treatment,” Proceedings of the National Academy of Sciences, online 16 June 2025, doi: 10.1073/pnas.2427211122.

Keywords: Neuroblastoma, Cancer, Antioxidant Enzymes, PRDX6, GSTP1, Differentiation Therapy, Childhood Cancer, Oncology, Pediatrics, Cancer Cells, Pharmacology, Drug Research