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Methoxsalen

Sampling of 2 samples on the extracorporeal photochemotherapy circuit, before and after sensitization with 8-MOP and UVA irradiation (without additional puncture)

Samples collection

Charline VAUCHY, PhD

Charline Vauchy, PhD

Thomas CREPIN, MD

The objective of this study is to describe the type of cell death induced by extracorporeal photochemotherapy, depending on the cell type, using a panel of complementary analysis techniques.

Extracorporeal photochemotherapy (ECP) is a cell therapy used for its immunomodulation and tolerance induction capabilities. Its main indications are the control of graft-versus-host (GVH) disease in hematopoietic cell allografts, treatment and control of rejection in solid organ transplantation and the treatment of cutaneous T-cell lymphoma. Data on the mechanisms of action of ECP remains very patchy. This lack of data limits the discussion on therapeutic regimens by disease.

ECP consists of repeated apheresis sessions to collect leukocytes from the patient. The cells are then photosensitized, irradiated with UVA and reinjected into the patient in a closed circuit. In the context of GVH, induced cell death would stimulate the expansion of regulatory cells (Treg), restore a Th1/Th2 balance and decrease Th17 polarization. The ECP also allows the expansion of Treg in solid organ transplantation. Conversely, ECP would restore or activate an antitumor immune response in cutaneous T lymphoma.

The type of cells collected and treated would play a major role in the effects obtained. However, these hypotheses must be consolidated, in particular by detailing the initial role of cell death. Several questions remain, on the chronology of cell death in the different treated subpopulations, on the uptake by phagocytes, but especially on the type of cell death induced according to the cell type (necroptosis, apoptosis, pyroptosis, autophagy). The data generated will allow for validation or detail of the mechanisms of resolution of the inflammation and/or the anti-tumour effect observed.

MORPHEE : Mechanisms of Cell Death Induced by Extracorporeal Photochemotherapy

MLKL (mixed lineage kinase domain-like pseudokinase) phosphorylation in Western blot

Centre Hospitalier Universitaire de Besancon

Head and Neck Neoplasms

Micronutrients

Mineral

Copper

Copper Supplement

5 samples collected for each patient (tumor biopsy, healthy tissue around the tumor, blood, urine and saliva), quantification of isotopes, measure of mRNA expression of proteins 4 samples for each patient (healthy tissue, blood, urine and saliva), quantification of isotopes, measure of mRNA expression of proteins

Emmanuel Bartaire, PhD

The distribution of stable (non-radioactive) isotopes in living organisms is increasingly studied, in particular the zinc (Zn), copper (Cu) and iron (Fe), not only in primitive organisms, but also in mammals.

The scientific community shows a growing interest in the study of the isotopic distribution of Cu in humans: this distribution can vary according to gender or nutrition. Concerning pathology, the isotopic distribution of Cu seems interesting in Wilson's disease or in cirrhosis.

Additionally, a promising area of study focuses on the role of Cu in cancerous tumors, neoangiogenesis, the mechanisms of free radicals reduction and signaling pathways.

Head and neck cancers are sensitive to platinum salts. Links between platinum and Cu are important: platinum penetrates into the cell through a Cu receptor, it interacts with the regulation mechanisms of Cu and platinum.

Preliminary studies suggest a variation of the measurable isotopic distribution of Zn in patients with breast tumor and of Cu in patients presenting breast as well as colorectal tumors.

The Larner et al. study suggest a promising role of Zn in breast cancer, indeed, results highlight a variation of distribution of Zn in 10 breast tumors. Concerning the study of Télouk et al. on 8 patients presenting colorectal tumors and 20 patients presenting breast tumors, results are in favor of an increase of mortality when Cu 65 is decreased in the serum and the isotopic modifications happen earlier than usual modifications of biochemical tumor markers such as: carbohydrate antigen (CA) 19.9, Carcinoma Antigen (CA) 15.3, Carcinoembryonic antigen (CEA).

Currently, there is no information about the distribution of the stable isotopes of Cu in head and neck tumors.

The objective of the study is to determine if the distribution of 65Cu / 63Cu is modified in tumoral tissues compared to healthy tissues. The isotopic distribution of the Cu in 2 tumor types, head and neck tumors and lymphomas, will be also investigated in order to determine if this distribution is specific of a tumor type or not.

In case of positivity of this variation, the prognostic interest of these parameters will be evaluated.

Blood Urine Saliva cancer tissue healthy tissue

Study of Copper Isotope in Head and Neck Cancer

Study of the ISotopic Repartition of cOpper in Head and Neck TumOral and lymPhomatous pathologiEs

Ecole Normale Supérieure de Lyon

Lille Catholic University

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
MORPHEE : Mechanisms of Cell Death Induced by Extracorporeal Photochemotherapy	NCT05333367	Cutaneous T-Cel... Graft Vs Host D... Graft Rejection	Samples collect...	18 Years - 85 Years	Centre Hospitalier Universitaire de Besancon
Study of Copper Isotope in Head and Neck Cancer	NCT02864836	Head and Neck T...	Samples collect...	18 Years -	Lille Catholic University
MORPHEE : Mechanisms of Cell Death Induced by Extracorporeal Photochemotherapy	NCT05333367	Cutaneous T-Cel... Graft Vs Host D... Graft Rejection	Samples collect...	18 Years - 85 Years	Centre Hospitalier Universitaire de Besancon
MORPHEE : Mechanisms of Cell Death Induced by Extracorporeal Photochemotherapy	NCT05333367	Cutaneous T-Cel... Graft Vs Host D... Graft Rejection	Samples collect...	18 Years - 85 Years	Centre Hospitalier Universitaire de Besancon
Study of Copper Isotope in Head and Neck Cancer	NCT02864836	Head and Neck T...	Samples collect...	18 Years -	Lille Catholic University

Spots Global Cancer Trial Database for samples collection