The journal Scientific Reports has published the article “Oncolytic alphavirus-induced extracellular vesicles counteract the immunosuppressive effect of melanoma-derived extracellular vesicles”, whose lead authors are Dr. Darshak Bhatt and Dr. Luciana Nogueira de Sousa Andrade.
The article addresses oncolytic virotherapy, a promising cancer treatment strategy that employs native or genetically modified viruses to infect and destroy cancer cells. It also explores extracellular vesicles, which are lipid membrane-enclosed particles released by cells that transport proteins, RNA, lipids, and other molecules, playing a key role in intercellular communication.
Speaking to the C2PO, Dr. Luciana Andrade explained that macrophages and lymphocytes are present in tumor tissues and receive signals carried by extracellular vesicles released by cancer cells. In some cases, these signals instruct the immune system that cancer cells pose no threat to the body. However, oncolytic virotherapy can modify the messages within extracellular vesicles, allowing the immune system to recognize and attack cancer cells. The communication between oncolytic virus-infected tumor cells and immune cells via extracellular vesicles remains poorly understood.
The researchers conducted oncolytic virotherapy using Semliki Forest virus-based replicons (rSFV) to treat metastatic melanoma cells in vitro. These viral particles were produced in the laboratory and genetically modified to prevent them from generating new infectious particles, ensuring the study adhered to biosafety regulations.
Their findings demonstrated that melanoma cells infected with replicons secreted extracellular vesicles with a distinct biochemical profile and microRNA content, which did not suppress immune cells as tumor-derived vesicles typically do. The researchers observed that extracellular vesicles from murine melanoma cells have the potential to suppress splenocyte proliferation and induce regulatory macrophages that promote tumor progression. However, vesicles from replicon-infected cells did not produce these effects. This led the researchers to conclude that rSFV infection induces changes in the immunomodulatory properties of melanoma-derived extracellular vesicles, potentially slowing tumor growth. The study underscores the significance of extracellular vesicles as modulators of the tumor microenvironment, which could enhance therapeutic efficacy.
Dr. Luciana Andrade also highlighted the importance of adjuvant therapies for cancer treatment—combining multiple therapeutic approaches to maximize beneficial effects and improve outcomes. In the future, the goal is to integrate modified extracellular vesicles, as well as those produced in response to replicons, with other treatment strategies.
Professor Roger Chammas commented on the study: “This research exemplifies how biotechnology can be applied to cancer treatment through the use of genetically modified viruses. It also highlights the value of deciphering the messages within extracellular vesicles, a promising field. Above all, the study reinforces the importance of continued scientific investigation in advancing cancer therapies.”
Dr. Darshak Bhatt has been researching oncolytic viruses for over a decade and earned a dual Ph.D. from the Universidade de São Paulo and the University of Groningen. He conducted the first part of his doctoral research at the Center for Translational Research in Oncology (CTO), a laboratory complex based at the Instituto do Câncer do Estado de São Paulo (ICESP) and affiliated with the Faculdade de Medicina da Universidade de São Paulo (FMUSP). At the CTO, he was part of the research team led by Prof. Roger Chammas and Dr. Luciana Andrade. After his studies at USP, he continued and completed his Ph.D. at the University of Groningen in the Netherlands. The full Ph.D. thesis of Dr. Darshak Bhatt can be accessed through the Groningen University website. Dr. Bhatt gave an interview to the C2PO about his experience with the dual Ph.D. and his time at USP.
Dr. Luciana Andrade completed her academic training at USP, from her undergraduate degree in Biology to her Master’s and Ph.D. in Oncology at FMUSP. A researcher at the CTO of ICESP/FMUSP for 13 years, she investigates the role of tumor-derived extracellular vesicles in therapeutic outcomes, immune system reprogramming within the tumor microenvironment, and tumor progression.
The article’s co-authors include Prof. Roger Chammas (CTO/ICESP/FMUSP), Prof. Toos Daemen (Groningen), Prof. Patricia Pintor Reis (UNESP), Dr. Alexis Germán Murillo Carrasco (CTO/ICESP/FMUSP), Dr. Andreia Otake (CTO/ICESP/FMUSP), Dr. Annemarie Boerma (Groningen), and Dr. Silvina Odete Bustos (CTO/ICESP/FMUSP).
In September 2025, CTO researchers, led by Prof. Roger Chammas and Dr. Luciana Andrade, will conduct the course Extracellular Vesicles in Oncology: A Systems Biology Approach, for South American students.
