By displaying that every subtype of germ cell tumor in kids has its personal immune signature, the research paves the best way for customized remedies which might be more practical and fewer poisonous for kids. Credit score: Hospital de Amor
A research performed by the Molecular Oncology Analysis Heart (CPOM) at Hospital de Amor in Barretos (previously Barretos Most cancers Hospital) within the state of São Paulo, Brazil, has recognized attainable biomarkers that might information the event of extra customized therapies for pediatric germ cell tumors (GCTs).
Though GCTs account for under 3% of childhood cancers, they problem docs and researchers attributable to their range and the toxicity of accessible remedies.
The paper is printed within the journal Frontiers in Immunology.
The principle method at present includes surgical procedure mixed with chemotherapy. Whereas efficient in lots of instances, this protocol just isn’t equally efficient for all tumor subtypes and may trigger long-term unwanted effects.
For that reason, researchers at Hospital de Amor determined to analyze the “immune environment” of GCTs. In different phrases, they aimed to grasp how a affected person’s immune cells work together with tumor cells. Their objective was to determine patterns explaining why some tumors are extra aggressive than others and to determine new therapeutic targets, particularly these linked to immunotherapy.
“Germ cell tumors can occur in adults as well as children and adolescents. In the pediatric population, they’re very rare, accounting for about 3% of tumors. Due to their rarity and heterogeneity, they’re difficult tumors to study,” explains Mariana Tomazini, research advisor and researcher on the CPOM.
Based on Tomazini, GCTs can come up in numerous places, together with the ovaries, testicles, central nervous system, and retroperitoneum. They’ll additionally current as completely different histological sorts, that are variations in mobile look and progress sample.
“It’s like a ‘signature’ of the tumor, a surname. This is because within the same organ, we can have tumors with different characteristics. This subtype, or histological type, helps doctors define the diagnosis and choose the best treatment strategy,” says Tomazini.
The analysis was performed as a part of Lenilson Silva’s grasp’s challenge. Silva analyzed samples from 17 pediatric sufferers identified with germ cell tumors between 2000 and 2021. Of these, 11 had been ovarian, three had been testicular, and three had been within the central nervous system. 4 regular, tumor-free tissues had been additionally used for comparability.
The scientists evaluated the expression of roughly 800 immune system-related genes and the presence of several types of immune cells infiltrating the tumors based mostly on the tissue samples. They then in contrast these knowledge with gene expression knowledge from grownup tumors in public databases, on the lookout for similarities and variations between age teams.
Tomazini explains that the objective was exactly to grasp how the immune system behaves in every sort of tumor.
“From this analysis, we saw that different histologies have a distinct immune profile. This helps to better characterize the tumor, understand why some are more aggressive, and at the same time, identify possible therapeutic targets. It paves the way for future studies focused on immunotherapy,” she says.
Distinct immunological profiles
The research revealed that every tumor subtype has its personal immune profile, performing as a “biological signature” that may affect medical habits and response to therapy.
For instance, the microenvironment of dysgerminomas (ovarian tumors) proved to be “immunologically active,” with a major presence of T lymphocytes, significantly CD8+ cells, which might assault diseased cells. Conversely, these tumors exhibited a rise in immune checkpoint molecules, together with CTLA-4, TIGIT, and IDO1, which hinder the immune response.
This implies that dysgerminoma could reply properly to immune checkpoint inhibitors, that are already used to deal with some grownup cancers, reminiscent of melanoma and lung most cancers.
“This histological type, for example, had a higher number of cytotoxic T cells. This explains why it’s usually a less aggressive tumor with a good response to treatment and active defenses in the body,” the researcher feedback.
Endodermal sinus tumors (yolk sac tumors, or YSTs), however, exhibited a extra immunosuppressive surroundings. Their T lymphocytes had been exhausted and fewer environment friendly at preventing the tumor. Moreover, they’d excessive ranges of CD24 and PVR, that are molecules related to immune evasion and resistance to chemotherapy. These molecules are additionally linked to extra aggressive tumors.
“In this subtype, the defense cells recognize the tumor but are unable to act as effectively. This helps explain why YSTs are more aggressive,” Tomazini explains.
A rise in CD24 was additionally noticed in one other subtype analyzed, embryonic carcinomas. Earlier research have prompt that blocking CD24 might assist restore sensitivity to chemotherapy.
“CD24 was a major finding. It’s been studied as a tumor cell marker in different cancers. If we can block its action, we may be able to reduce tumor progression or even facilitate the immune system’s recognition of diseased cells,” Tomazini explains.
Blended tumors of the central nervous system, however, confirmed fewer vital modifications, which can be linked to mobile range or the diminished variety of samples.
Why does it matter?
The outcomes present that every subtype of germ cell tumor in kids has its personal immune signature. Based on the scientist, this discovering paves the best way for extra individualized remedies.
“This means that it’s useless to apply the same generic treatment to all GCTs. Each patient has a tumor with a distinct immune profile. And, because we’re dealing with children, the more options that are less aggressive and have fewer long-term side effects, the better,” the researcher argues.
As a result of it’s a uncommon most cancers, the research concerned solely 17 sufferers, a small quantity in statistical phrases. Moreover, not all histological subtypes had been represented. Nonetheless, the outcomes are thought of a pioneering first step. The group intends to validate the findings in multicenter research with a bigger variety of samples and transfer ahead with medical trials testing particular immunotherapies for the completely different subtypes.
“This is the key issue in our study: the search for new biomarkers that can identify germ cell tumors and their subtypes in order to achieve a more accurate and specific diagnosis. Then, we can consider more appropriate targeted therapies or immunotherapies. Knowing what differentiates each tumor allows us to consider personalized treatments that are more effective and less toxic for children,” Tomazini concludes.
The research gained the award for greatest paper on the Latin American Society of Pediatric Oncology (SLAOP) convention held in Colombia this 12 months. The occasion promotes interdisciplinary scientific growth in pediatric oncology and hematology, in addition to enhancing requirements of care and medical growth for kids and adolescents with most cancers.
Extra info:
Lenilson Silva et al, Immune profiling of pediatric germ cell tumors identifies key cell populations and novel therapeutic targets, Frontiers in Immunology (2025). DOI: 10.3389/fimmu.2025.1579948
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Research identifies candidates for therapeutic targets in pediatric germ cell tumors (2025, September 19)
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