To grow, a tumor must achieve the impossible: convince our immune system NOT to destroy it.

How does it do it? With an ancient and ingenious theft.

It browses an archive hidden in our own DNA. It reactivates the same genetic programs that allowed us, as embryos, to build the placenta, invade the uterus, create new blood vessels and temporarily switch off the mother’s immune defenses.

What in the embryo is a project for life, in the tumor becomes a project for survival.

From an immunological point of view, the embryo is a semi-transplant. Half of its DNA is paternal, therefore foreign to the mother. Yet it is not rejected. The placenta and trophoblast create a bubble of tolerance around it that reprograms maternal defenses.

Cancer does exactly the same.

Cancer cells learn to express molecules like PD-L1 and HLA-E. They are powerful STOP signals for T lymphocytes and Natural Killer cells. In practice, they tell the immune system: “I am not a danger”. They create a local immune paralysis.

This insight led to the study by Bambino Gesù Children’s Hospital, published in Signal Transduction and Targeted Therapy.

Researchers engineered a new generation of genetically enhanced Natural Killer cells to break this deception.

NK cells are our first line of defense against viruses and tumors, but they are switched off inside the tumor microenvironment. The new multifunctional platform makes them resistant with 3 combined strategies.

We are still in the preclinical phase, further studies are needed before clinical use, but the message is powerful: to defeat cancer, it is not enough to boost our defenses. We must prevent it from reactivating those ancestral programs born to protect new life and that it has turned into a weapon for its own survival.

Source: Bambino Gesù Children’s Hospital – Signal Transduction and Targeted Therapy

However, 2 landmark studies presented at the 2025 ASCO Annual Meeting may signal a pivotal shift in the management of locally advanced, resectable HNSCC.

Key Points:

• The standard of care for locally advanced head and neck squamous cell carcinoma (HNSCC) has remained unchanged for decades, but 2 landmark studies presented at the 2025 ASCO Annual Meeting may signal a pivotal shift in the management of this disease.
• In the NIVOPOSTOP trial, the addition of nivolumab to postoperative cisplatin-based chemoradiation significantly improved disease-free survival (DFS) in patients with resected, high-risk, locally advanced HNSCC.
• Data from the KEYNOTE-689 trial show that perioperative pembrolizumab in patients with resectable, locally advanced HNSCC significantly improved median event-free survival (EFS) when added to standard-of-care surgery and chemoradiation.

The NIVOPOSTOP and KEYNOTE-689 trials represent a breakthrough in the management of resected, locally advanced HNSCC, marking the first phase 3 evidence to show meaningful improvements in DFS and EFS with the addition of immune checkpoint inhibitors to standard treatment.

Authors: Maria A. Velez, MD; Coral Olazagasti, MD; and Ana Velazquez, MD, FASCO

Full article: https://dailynews.ascopubs.org/do/new-era-immunotherapy-treatment-locally-advanced-head-and-neck-squamous-cell-carcinoma

A chimeric antigen receptor (CAR) sprouts from the surface of a genetically reengineered white blood cell.

The receptor is a manufactured protein, and designed by molecular biologists to seek out and interact with specific antigens appearing on cancer cells.

Now empowered with CAR, these killer T-cells are infused into the patient to attack and kill cancer cells.

Cancer immunotherapy is a rapidly growing field that is showing incredible promise.

Numerous clinical trials are underway.

Animation credit: hybridmedical

In a recent study published in Nature Medicine, researchers report the successful treatment of a neuroblastoma patient with chimeric antigen receptor (CAR) T-cell therapy.

A woman, now twenty-three years old and with two children,
treated in 2006, with a pioneering type of immunotherapy for a solid tumour has been in remission for more than 19 years with no further treatments.

In CAR-T-cell therapy, T-cells are isolated from the patient’s blood and genetically engineered to express CARs on their surface. When administered to the patient, CAR-T-cells recognize and facilitate the clearance of cancer cells by binding to specific proteins on their surface.

Although CAR-T-cell therapy has been widely successful in treating hematological cancers, this treatment approach is limited in its ability to combat solid tumors.

Neuroblastoma is a rare solid tumor that develops in immature nerve cells. This type of cancer primarily affects children five years of age and younger and is associated with high relapse rates.

Between 2004 and 2009, the researchers of the current study conducted a phase I clinical trial. During this trial, activated T-cells were engineered to target disialoganglioside 2 (GD2), a protein often overexpressed in neuroblastoma cells. This therapy involved both activated T-cells (ATCs) and Epstein-Barr virus (EBV)- specific T-cells (VSTs), which were trained to recognize and attack tumor cells.

The trial enrolled a total of 19 children, 11 of whom had active relapsed neuroblastoma. Among eight patients with no evidence of active disease, five had a history of relapsed disease, and three were infused with the GD2 CAR-T cell therapy after completing therapy for high-risk disease.
Among eleven patients with active disease at the time of infusion, three had complete responses, and one had a partial response. One of the three patients with complete responses subsequently experienced disease relapse. However, the remaining two patients had sustained responses. One experienced beneficial effects for eight years until being lost to follow-up, while the other continued to report positive outcomes for more than 18 years.

Source:

https://www.nature.com/articles/s41591-025-03513-0

https://www.news-medical.net/news/20250217/Cancer-free-for-18-years-CAR-T-therapy-sets-new-milestone-in-neuroblastoma-treatment.aspx