[Un article de The Conversation écrit par Adèle de Masson – Professeur en dermatologie, Université Paris Cité]
Unlike ganglionic lymphomas (Hodgkin lymphoma and non -hodgkinian lymphomas) which mainly affect lymph nodes, skin T lymphomas are initially developing in the skin. They can manifest themselves in different clinical forms, ranging from plates and red spots to nodules and tumors.
The skin T lymphomas are classified into several subtypes, the most common being fungid mycosis. These diseases often evolve indolent at first but can progress towards more aggressive and systemic stages if they are not adequately treated.
A low impact but increasing
Few of skin T lymphomas affect approximately 1 in 100,000 adults each year. But their incidence has increased over the past thirty years. This is possibly linked to a better knowledge of these pathologies – and, therefore, an increase in diagnosis – but also with the aging of the population and potential environmental factors, a role of pesticides having been suspected on the basis of epidemiological studies.
Although most patients diagnosed at an early stage of the disease can manage their symptoms for life, around 20 % are progressing towards an advanced stage which is characterized by an extended skin disease, damage to lymph nodes, visceral organs or significant blood damage.
Resistance to treatments in certain patients
The precise diagnosis is based on the histopathological examination of skin lesions (after biopsy), supplemented by what are called immunophenophenotypic and molecular tests. In summary, after biopsy, we first look at the form of cells under the microscope. Then, we carry out “identity tests” to see which markers carry these cells and, finally, we analyze their DNA to verify if they all come from the same abnormal clone.
The treatment of skin T lymphomas depends on the stage of the disease, its severity and the individual characteristics of the patient, and may include options such as:
- Phototherapywhich is based on the use of ultraviolet rays in the cabin with doses and lengths of controlled waves;
- Topical chemotherapywhich are gels containing chemotherapy, applied to the skin;
- immunotherapywhich rely on monoclonal antibodies which use the immune system to fight against tumors;
- targeted therapies and bone marrow transplantsin advanced cases.
Current treatments, including monoclonal antibodies immunotherapy, can cause resistance, whether primary – lack of response from the start of treatment, or secondary – loss of efficiency after an initial response. These phenomena have been observed in the randomized trials of Mavoric (Mogamulizumab) and Alcanza (Brentximab vedotin).
The problem concerning this disease therefore lies in the ability to control it over the long term.
A new candidate to treat skin T lymphomas
It is in this perspective that the Sprint project is part, for “synergy to accelerate therapeutic innovation in skin T lymphomas”. Led by an international research team, this project made it possible to highlight a promising new candidate for the treatment of advanced skin T lymphomas: the CCR8 receiver.
The CCR8 receiver plays a key role in the microenvironment of the tumor and could therefore represent a strategic therapeutic target. It is indeed present on the surface at the same time:
- of a special subpopulation of T cell cells which play an essential role in the maintenance of immune tolerance (T lymphocytes intratimoral regulators, or TREG).
The regulatory T lymphocytes play a crucial role in preventing autoimmune diseases by controlling and repressing excessive or non-specific immune responses against the body's own tissues. (In autoimmune diseases, the immune system dysfunction and attacks the normal constituents of the organism, editor's note).
- of malignant cells of skin T lymphomas.
In the context of cancers such as skin T lymphomas, T lymphocytes intratimoral regulators (TREG) can be recruited in cancer lesions and contribute to the creation of an environment that will promote the growth and survival of tumor cells.
The presence of these cells in the tissues affected by cancers can be associated with faster progression of the disease and a less favorable response to treatments.
Consequently, target the T lymphocytes intratimoral regulators (TREG) – via The CCR8 receiver present on their surface – and modulating their function represents a therapeutic strategy to strengthen the capacity of the immune system to recognize and eliminate tumor cells.
The discovery of the role of the CCR8 receptor expressed on the surface of these cells opens up new perspectives for the development of combined treatments aimed at targeting both malignant cells and tumor microenvironment.
Clinical trials specifically targeting the CCR8 receiver are scheduled soon to assess their effectiveness in the management of advanced skin T lymphomas resistant to existing treatments.
Promising results also for other lymphomas and cancers
Interestingly, these results could make it possible to advance in the development of this drug which could prove useful not only in skin T lymphomas, but also in other T lymphomas like lymph node, or even cancers in general, due to the role of the CCR8 receiver in the regulation of immune responses against cancer.
In conclusion, the target of the CCR8 receptor represents a significant advance in the understanding and treatment of advanced skin T lymphomas.
Continuous efforts in this direction are essential to develop more efficient and personalized therapeutic strategies, capable of overcoming the challenges posed by treatment for treatment and improving results for patients.
With an unwavering passion for local news, Christopher leads our editorial team with integrity and dedication. With over 20 years’ experience, he is the backbone of Wouldsayso, ensuring that we stay true to our mission to inform.
