A group of lymphocytes activates a response able to destroy tumours

Formación de una sinapsis inmune (activación de linfocito T CD8+ por parte de un linfocito T CD4+P, que ha capturado bacterias que expresan un antígeno reconocido por el T CD8+) Formación de una sinapsis inmune (activación de linfocito T CD8+ por parte de un linfocito T CD4+P, que ha capturado bacterias que expresan un antígeno reconocido por el T CD8+) Esteban Veiga, CNB-CSIC

A study published in Nature Communications indicates that CD4+ T lymphocytes are able to act as antigen-presenting cells. This function could be exploited to develop a new generation of immunotherapies against cancer. This technology is protected by patent and has a business project to bring it to the market.

A team of researchers led by Esteban Veiga, of the Centro Nacional de Biotecnología of the CSIC (CNB-CSIC), has discovered that a group of immune system cells termed CD4+ T lymphocytes can activate a response able to destroy several types of tumours. This finding, published in the journal Nature Communications, has been protected by patent and has considerable commercial potential in the development of a new generation of cancer immuntherapeutics.

The study showed that, in contrast to one of the dogmas of immunology, CD4+ T lymphocytes can capture and destroy bacteria. In addition, they can behave as antigen-presenting cells, which strongly activate other lymphocytes (CD8+ T cells) with the potential to destroy various tumor types. When CD4+ T lymphocytes act as antigen-presenting cells, they are called tpCD4+.

"In this study, we not only described a new lymphocyte function, but found a way to make use of this discovery. We show that it could be useful in the battle against cancer. We will continue work on this project to one day make it a reality," says Veiga.

The scientist cautions that, to carry out this anti-tumour function, CD8+ T lymphocytes must first be activated and must also withstand the hostile environment generated by solid tumours. "Until now it was thought that the task of activating CD8+ T lymphocytes was exclusive to a type of antigen-presenting cells called dendritic cells," adds Veiga.

Potential for a new generation of immunotherapeutics

The study shows that this discovery can be applied in clinical practice. "Using an aggressive mouse melanoma model, we found we can use these CD4+ T lymphocytes (which captured bacteria genetically modified to express a tumour antigen) to protect very effectively against tumour formation," says Veiga.

"In support of these data, we also observed that the CD8+ T lymphocytes that are activated by contact with tpCD4+ lymphocytes end up being central memory lymphocytes (involved in the fight against tumours), which also express very small amounts of PD-1," Veiga explains. "Note that the most successful cancer immunotherapies in recent years are based on antibodies against PD-1 or its ligand, so this technology/discovery also covers the gap left by these cancer strategies," he concludes.

These results highlight the potential of CD4+ T lymphocytes as a new generation of cancer immunotherapies. In addition to demonstrating its usefulness in a cancer model, a patent has been applied for and a project is being developed with a technology-based company to take it to market, with the support of the Unit for the Protection of Results and Promotion of Technology-Based Companies of the CSIC Deputy Vice-Presidency of Knowledge Transfer (VATC).

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