BUFFALO, NY - June 17, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on June 10, 2025, titled “Exceptional responders to immunotherapy in pancreatic cancer: A multi-institutional case series of a rare occurrence.”

The study, led by first author Kavin Sugumar and corresponding author Jordan M. Winter, from University Hospitals Seidman Cancer Center, reports on a rare group of pancreatic cancer (PC) patients who responded remarkably well to immunotherapy, a treatment typically considered ineffective for this cancer type. The analysis, which includes data from 14 patients across multiple U.S. institutions, identifies outcomes that could help refine treatment strategies for one of the most aggressive and deadly forms of cancer.

“Between 2020–21, 471 oncologists from 91 major cancer centers in the United States were contacted.”

Pancreatic cancer has among the lowest survival rates and few effective therapies. While immunotherapy has transformed the treatment landscape for several other cancers, it generally offers little benefit for pancreatic cancer. However, this study highlights a small but important group of patients who experienced significant and sustained responses to immune-based treatment without chemotherapy. Most had advanced or metastatic disease and had already progressed after standard treatments.

Among the 14 patients, 82% had partial tumor shrinkage, and nearly one-third had a notable decrease in tumor markers. The median progression-free survival was 12 months, and most patients were still alive at follow-up, with survival rates of 80% at one year and 70% at two years. These outcomes contrast sharply with standard therapies, which often provide only a few months of benefit for similar patients.

Interestingly, while some patients had high microsatellite instability (MSI-high)—a known marker for immunotherapy success—more than half did not, suggesting other biological mechanisms may be involved. This result highlights the need for new biomarkers to be discovered to predict treatment response in future studies.

This case series is the largest focused exclusively on exceptional immunotherapy responders in pancreatic cancer. By excluding patients who received chemotherapy, the study isolates the effects of immune-based drugs, including PD-1 inhibitors such as pembrolizumab and nivolumab, CTLA-4 inhibitors like ipilimumab, and agents targeting macrophages.

While the sample size is small, the findings challenge the assumption that immunotherapy is ineffective for nearly all pancreatic cancer patients. The study suggests that, under certain biological conditions, this treatment can be remarkably successful. Further research is needed to understand the underlying mechanisms.

This work supports the need to reconsider how clinical trials are designed for pancreatic cancer and who is eligible for immunotherapy. Broader criteria and more personalized molecular profiling could help uncover hidden opportunities for treatment in this highly lethal cancer.

DOI - https://doi.org/10.18632/oncotarget.28739

Correspondence to - Jordan M. Winter - jordan.winter@UHHospitals.org

Video short - https://www.youtube.com/watch?v=VeWTcuVmqgM

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Oncotarget

Rare Pancreatic Cancer Patients Show Strong Response to Immunotherapy

Dr. Amparo Santamaria describes a #research paper she co-authored that was #published in Volume 17, Issue 6 of Aging (Aging-US), titled “Enhancing oocyte activation in women with ovarian failure: clinical outcomes of the Stem Cell Regenera study using G-CSF mobilization of peripheral blood stem cells and intraovarian injection of stem cell factor-enriched platelet rich plasma in real-world-practice.”

DOI - https://doi.org/10.18632/aging.206274

Corresponding author -Amparo Santamaria - Amparo.santamaria@ivirma.com

Video interview - https://www.youtube.com/watch?v=oRFJNwnXZWI

Abstract

The study assesses the effectiveness and safety of the Stem Cell Regenera Treatment for oocyte activation in women with ovarian failure, including conditions such as Poor Ovarian Response (POR), Diminished Ovarian Reserve (DOR), and Premature Ovarian Insufficiency (POI). This retrospective observational study was conducted from January 2023 to December 2024 at the IVIRMA Alicante Clinics in Spain.

Women diagnosed with ovarian failure participated in the study, which involved mobilizing Hematopoietic Stem Cells from bone marrow into peripheral blood using granulocyte colony- stimulating factor (G-CSF). This was followed by an intraovarian injection of Stem Cell Factor- enriched Platelet Rich Plasma (SCFE-PRP).

The primary outcome measures were the rate of oocyte activation, leukocytes and stem cell count, and pregnancy rates. Oocyte activation was defined as an increase in total Antral Follicle Count of three or more follicles after treatment and/or at least a 20% rise in Anti-Müllerian Hormone levels. Safety was assessed based on adverse effects. Pregnancy rates were evaluated for both spontaneous gestation and following in vitro fertilization (IVF) treatment.

A total of 145 women participated: the overall activation rate was 68.28%, with 7.07% achieving spontaneous gestation and 14.14% achieving pregnancy following IVF. Mobilization of CD34+ cells was successful in all participants, with an average collection of 32.96 CD34+ cells/μl. No severe adverse effects were observed. The study concluded that the Stem Cell Regenera Treatment is effective and safe for oocyte activation in women with ovarian failure in real-world practice.

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Keywords - aging, Stem Cell Regenera, oocyte activation, ovarian regeneration, G-CSF, SCFE-PRP, ovarian failure

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Aging (Aging-US)

Behind the Study: Enhancing Oocyte Activation in Women with Ovarian Failure

Futurist and Berkeley Divinity at Yale alum Rachel Hatch (‘08) joins Brandon and Hannah for a conversation about how to look for signals of change within our own parishes and communities as we make thoughtful choices for the future. In this episode, Rachel encourages leaders to cultivate a practice of imagining possibilities and taking steps toward hope-filled futures, while still addressing the urgencies of the present.

57: Forecasting the Future with Rachel Hatch

BUFFALO, NY — July 15, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 6, on June 5, 2025, titled “Senescence caused by telomerase inactivation in myeloid, mesenchymal, and endothelial cells has distinct effects on cancer progression.”

In this study, first author Joseph Rupert, along with corresponding author Mikhail G. Kolonin and colleagues from The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, McGovern Medical School, at The University of Texas Health Sciences Center at Houston, investigated how aging-related changes in different cell types affect cancer progression. By turning off telomerase in specific cell populations in mice, the researchers discovered that cell aging, or senescence, can slow primary tumor growth but also trigger unexpected effects. This work sheds light on the complex relationship between aging cells and cancer and may help guide future anti-cancer strategies.

The team used genetically modified mice to deactivate telomerase, the enzyme that maintains chromosome ends, specifically in immune, connective tissue, and blood vessel cells. This caused these cells to enter a state of senescence, where they stop dividing and release inflammatory signals. The researchers then implanted breast, prostate, and pancreatic cancer cells into the mice and tracked how tumors developed. They found that when telomerase was inactivated in immune cells or connective tissue cells, tumors grew more slowly. However, these tumors showed signs of increased tissue damage and potential aggressiveness.

Interestingly, when telomerase was turned off in endothelial cells, which cover blood vessels, tumors shrank and became poorly supplied with blood, leading to oxygen deprivation. In the case of pancreatic cancer cells, this low-oxygen environment made them more likely to spread to the liver, highlighting a potential risk of targeting these cells.

“[…] this study shows that senescence and metabolic dysfunction resulting from telomerase inactivation in distinct cells in the tumor microenvironment have different effects on tumor growth and metastasizing of carcinomas.”

This research provides important insights into how aging cells within the tumor microenvironment (TME) influence cancer behavior. While senescence in certain cell types can help suppress tumor growth, it may also create conditions that favor cancer metastasis. These findings highlight the need to consider cell type-specific effects when developing therapies that target senescent cells. By mapping how different cell populations contribute to cancer progression in aging tissues, this study opens the door for more precise approaches to prevent both tumor growth and spread.

DOI - https://doi.org/10.18632/aging.206268

Corresponding author - Mikhail G. Kolonin - mikhail.g.kolonin@uth.tmc.edu

Video short - https://www.youtube.com/watch?v=py8wFKj7enE

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Keywords - aging, senescence, telomerase, myeloid, mesenchymal, endothelial

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How Telomerase Inactivation in Aging Cells Influences Cancer Growth and Metastasis

BUFFALO, NY - July 16, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on July 9, 2025, titled “A novel anti-human CD25 mAb with preferential reactivity to activated T regulatory cells depletes them from the tumor microenvironment.”

In this study, researchers from the National Institute of Allergy and Infectious Diseases, led by first author Maja Buszko and corresponding author Ethan M. Shevach, discovered a new monoclonal antibody that selectively targets a subset of immune cells called regulatory T cells (Tregs). These cells, while normally important for preventing autoimmunity, also can block the body’s ability to fight cancer by suppressing anti-tumor immune responses. This discovery could lead to novel cancer therapies that strengthen the immune system’s capacity to attack tumors.

The researchers identified an anti-CD25 monoclonal antibody with several atypical properties and named it 2B010.  To evaluate its effects, they used humanized mice, laboratory mice that are engineered to carry human immune cells, to closely mimic how human immune systems respond to cancer. The treatment of these mouse models with 2B010 significantly decreased the number of Tregs in tumors and boosted the activity of CD8+ T cells, which are essential for killing cancer cells. Importantly, 2B010 worked without disrupting other key immune functions. Unlike traditional Anti-CD25 antibodies, it did not interfere with interleukin-2 (IL-2) signaling, which is essential for the growth and activity of effector T cells that fight cancer. 

“2B010 also had no effect on IL-2 induced STAT5 phosphorylation or CD4+ T cell proliferation in vitro while both were blocked by Clone D1 further supporting the view that 2B010 does not recognize the IL-2 binding site.”

This finding is especially significant because high levels of Tregs in tumors are associated with poor outcomes in many cancers. By specifically removing these cells, 2B010 may help overcome one of the main barriers to current immunotherapy approaches. Its ability to preserve IL-2 signaling could also make it safer and more effective when used alone or in combination with existing therapies such as immune checkpoint inhibitors.

While the 2B010 antibody showed strong effects in reducing Tregs and boosting immune cell activity, the study did not observe changes in tumor size in these models. Researchers suggest this may be due to limitations in the preclinical systems used, such as the lack of tumor-specific T cells in humanized mice. Nevertheless, these findings demonstrate that 2B010 has a unique mechanism of action that could complement other cancer immunotherapies in future clinical trials.

In conclusion, the development of 2B010 is a promising step toward selectively disrupting the immune suppressive environment in tumors. As researchers continue to refine and test this antibody, it could become a powerful tool for enhancing the effectiveness of cancer treatments and improving outcomes for patients.

DOI - https://doi.org/10.18632/oncotarget.28752

Correspondence to - Ethan M. Shevach - eshevach@Niaid.NIH.gov

Video short - https://www.youtube.com/watch?v=2NJcGsI7WXA

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Keywords - cancer, Treg, CD25, TME, mAb, GVHD

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New Antibody Selectively Targets Immune Cells That Suppress Anti-Tumor Responses

BUFFALO, NY — July 17, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 6, on June 9, 2025, titled “Developing a quantitative estimate of muscle age acceleration by a novel phenotypic clock: cross-sectional study in healthy, middle-aged and older adults.”

In this study, led by first authors Lucia Ventura, Antonella Cano and Marco Morrone, along with corresponding author Franca Deriu from the University of Sassari, researchers introduce a new method to predict how muscles age, offering an early warning system for sarcopenia, the condition of age-related muscle loss. The study demonstrates how a simple, low-cost approach can identify middle-aged and older adults at higher risk for declining muscle health, allowing timely preventive strategies.

The researchers developed a tool called Muscle Age Acceleration (MAA), which measures how quickly an individual’s muscles are aging compared to their actual age. By analyzing physical performance tests and body composition in 215 healthy participants aged 50 to 90 years, the researchers found that about 25% of individuals experience accelerated muscle aging. These individuals had a higher probability of developing sarcopenia, despite appearing healthy and not yet having received a diagnosis of the condition.

Sarcopenia reduces muscle strength and physical performance, being a growing concern for older adults. It contributes to frailty, falls, and an increased risk of disability. Despite greater awareness, this condition often goes undetected until significant muscle loss occurs. This new muscular clock offers an opportunity to detect subtle changes in muscle health before they progress to more severe stages.

By using common tests such as handgrip strength, walking speed, and mobility assessments, the MAA tool can classify individuals as having accelerated, normal, or decelerated muscle aging. Those with accelerated muscle aging also showed small changes in blood markers, suggesting early and hidden inflammation linked to muscle decline. This finding indicates that MAA may act as both a predictor of muscle-related aging and an indicator of overall health risks.

“According to MAA, three trajectories were identified: accelerated agers displayed higher risk for sarcopenia (19%), as compared to normal (9%; p < 0.0001) and decelerated (2%; p < 0.0001), paralleled by significant subclinical alterations of haemato-chemical markers in accelerated agers.”

If validated in future studies, this innovative approach could transform how clinicians and caregivers screen for early signs of sarcopenia. Its simplicity makes it suitable for use in clinics and community settings, helping older adults maintain independence and quality of life as they age.

In summary, these findings highlight the importance of monitoring muscle health and physical performance in older adults. By detecting early signs of muscle aging with tools like MAA, interventions such as exercise and dietary changes can be introduced earlier, potentially delaying or preventing sarcopenia and its complications.

DOI - https://doi.org/10.18632/aging.206269

Corresponding author - Franca Deriu - deriuf@uniss.it

Video short - https://www.youtube.com/watch?v=kc9i0aJNNp0

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New Aging Clock Predicts Early Risk of Muscle Loss in Older Adults

BUFFALO, NY - July 18, 2025 – A new #editorial was #published in Volume 16 of Oncotarget on July 16, 2025, titled “microRNAs in soft tissue sarcoma: State of the art and barriers to translation.”

In this article, Elizaveta K. Titerina, Alessandro La Ferlita, and Joal D. Beane from Ohio State University discuss the role of microRNAs in soft tissue sarcomas (STS), a rare and diverse group of cancers that begin in connective tissues, like bone or fat. The authors explain how these small molecules regulate cancer-related processes and highlight their potential as non-invasive biomarkers for diagnosis and monitoring. They also outline the main challenges that need to be addressed before microRNA-based strategies can be used in clinical settings.

Soft tissue sarcomas include over 50 subtypes, making precise diagnosis and effective treatment difficult. The editorial describes how microRNAs influence cancer growth, spread, and response to therapies. Because microRNAs are stable in body fluids like blood and saliva, they could be used for early detection and to help guide treatment decisions. Such as, certain groups of microRNAs are linked to how patients respond to specific drugs, showing their potential as tools for precision medicine.

“For example, miR-17-92 and miR-106b-25 clusters have been associated with sensitivity or resistance to eribulin in STS.”

The authors also explain that microRNAs could help distinguish between tumor types that are often difficult to differentiate, such as benign lipomas and malignant liposarcomas. Recognizing these differences is crucial for guiding treatment decisions. Specific patterns of microRNA expression in blood samples may enable clinicians to make quicker and more reliable diagnoses without the need for invasive procedures. Beyond their diagnostic role, microRNAs are also being explored as therapeutic tools, but applying microRNA-based therapies to patients remains challenging. These molecules can act as either cancer promoters or suppressors, depending on the environment, which complicates the development of safe and targeted treatments. However, new delivery methods such as lipid nanoparticles show promise in improving precision and safety.

Overall, microRNAs are emerging as an important focus in STS research, offering new possibilities for advancing diagnosis, prognosis, and treatment. As researchers continue to address the current challenges, these small molecules could become valuable tools in improving cancer care.

DOI - https://doi.org/10.18632/oncotarget.28754

Correspondence to - Joal D. Beane, joal.beane@osumc.edu

Video short - https://www.youtube.com/watch?v=MlLGA8BObPQ

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Keywords - cancer, soft tissue sarcoma, liposarcoma, microRNA, small non-coding RNA, cancer biomarkers

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microRNAs Emerge as Biomarkers and Diagnostic Tools in Soft Tissue Sarcoma

In this episode, Brandon talks with New York Times bestselling author, public theologian, preacher, and founder of Sojourners, The Rev’d Jim Wallis. Their conversation explores the theological implications of authoritarianism, new frames for understanding church unity, and the difference between optimism and hope.

58: The Idolatry of White Nationalism with Jim Wallis

In this episode, host Rob Malley and guest Elhanan Miller discuss the power of religious and cultural dialogue in building bridges between Jewish and Muslim communities, and how Elhanan’s Arabic-language media project aims to foster empathy across deep political divides.

Rabbi Elhanan Miller is the founding director of People of the Book, an educational non-profit that explains Jewish faith and culture to Muslim audiences. His viral videos reach some 450,000 subscribers and millions of monthly hits, mostly in the Arab Middle East. Miller is a research fellow at the Shalom Hartman Institute in Jerusalem, specializing in Arab and Israeli politics and the intersection of Judaism and Islam. He regularly comments on Israeli affairs for international Arabic news channels, such as: BBC Arabic, Sky News Arabia, DW Arabic, France 24 Arabic, al-Mashhad (Dubai), and Israeli public news channel Makan. Miller previously served as the Arab Affairs Correspondent for The Times of Israel and as rabbi of the Jewish community in Canberra, Australia. Born and raised in Jerusalem, Miller began studying Arabic at 13. He completed his BA and MA degrees in Middle East History and Islamic Studies at Hebrew University.

You can find Elhanan and his work here:

https://www.youtube.com/@people.of.thebook 
https://www.facebook.com/peoplethebook/ 
https://www.instagram.com/people.of.thebook/

The host: Robert Malley is a seasoned diplomat and conflict resolution expert with decades of experience in international affairs. He has served in senior roles under multiple U.S. administrations, including as Special Envoy for Iran and as a lead negotiator for the Iran nuclear deal. He is a Senior Fellow at the Jackson School of Global Affairs and the founding director of the International Leadership Center’s Peace Hub. 

This episode is part of a 4-part interview series with Yale’s 2025 Peace Fellows. Find out more about the Yale Peace Fellowship here: https://jackson.yale.edu/international-leadership-center/peace-fellowship/


Episode 1: Building Bridges Between Jewish and Muslim Communities, with Rabbi Elhanan Miller

In this episode, host Yuval Ben-David and guest Mengistu Assefa Dadi explore the roots of conflict in the Horn of Africa, the decline of regional leadership, and the critical role of grassroots peacebuilding and local resilience in driving long-term stability.

Mengistu Assefa Dadi is an Ethiopian political and conflict analyst known for designing peace dialogue projects, managing initiatives that promote human rights, media freedom, and democratic governance, and implementing innovative strategies to address complex socio-political challenges in fragile states. Throughout his career, Mengistu has held roles at organizations such as the Center for Advancement of Rights and Democracy (CARD) in Ethiopia and has most recently been a Peace Fellow at Yale’s International Leadership Center. Mengistu holds a Master’s in Global Studies and International Relations and is pursuing another master's in African studies at Addis Ababa University.

You can connect with Mengistu on LinkedIn: www.linkedin.com/in/mengistuassefa-dadi

The host: Yuval Ben-David is Chief Strategy Officer at Yale’s International Leadership Center.
This episode is part of a 4-part interview series with Yale’s 2025 Peace Fellows. Find out more about the Yale Peace Fellowship: https://jackson.yale.edu/international-leadership-center/peace-fellowship/


Episode 2: Africa’s Leadership Crisis, with Mengistu Assefa Dadi

In this episode, host Robert Malley and guest Jaser AbuMousa talk about defining moments of Jaser’s life and work in Gaza, how he honors the memory of his wife and sons, and how he finds hope in continuing to work towards peace in the Middle East.

Jaser AbuMousa is a Palestinian political analyst and development specialist from Khan Younis, Gaza. He most recently served as a Program Manager for the Swiss Development Cooperation in the occupied Palestinian territory, where he managed humanitarian projects and authored biweekly reports on Gaza’s political, economic, and humanitarian dynamics. His career spans roles in engineering, social work, and political research, including with UNRWA and the EU-funded ‘Private Sector Reconstruction in Gaza’ program.

In October 2023, Jaser lost his wife Heba and two sons in an airstrike. Following the incident, he and his two surviving children spent over a year in the United Arab Emirates for medical treatment. As a Yale Peace Fellow, Jaser focused on postwar reconstruction strategies that reflect Palestinian priorities and mend Gaza’s torn social fabric.

You can connect with Jaser on socials:
https://www.linkedin.com/in/jaser-abumousa-9b01441a5/ 
https://x.com/jaser_hmaid

The host: Robert Malley is a seasoned diplomat and conflict resolution expert with decades of experience in international affairs. He has served in senior roles under multiple U.S. administrations, including as Special Envoy for Iran and as a lead negotiator for the Iran nuclear deal. He is a Senior Fellow at the Jackson School of Global Affairs and the founding director of the International Leadership Center’s Peace Hub.

This episode is part of a 4-part interview series with Yale’s 2025 Peace Fellows. Find out more about the Yale Peace Fellowship: https://jackson.yale.edu/international-leadership-center/peace-fellowship/

Episode 3: Finding Hope after Gaza, with Jaser AbuMousa

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.

Oncotarget is now indexed by MEDLINE, PubMed and PMC/PubMed.

Read about the Oncotarget Scientific Integrity Process: https://www.oncotarget.com/scientific_integrity/

Rare Pancreatic Cancer Patients Show Strong Response to Immunotherapy

Oncotarget Podcast

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