Cercetător Senior Carolina Constantin

Cercetător Senior Carolina Constantin

Victor Babeș” National Institute of Pathology, Immunology Laboratory & Colentina Clinical Hospital, Research Core of Pathology Department, Bucharest

Abordări proteomice pentru biomarkeri circulanţi în cancerul de piele
Autori: Carolina Constantin, Mihaela Surcel, Ana Caruntu, Sabina Zurac, Monica Neagu

Contextul imunologic in relatia gazda – celula tumorala joaca un rol cheie in evaluarea eficientei (imuno)terapiei anti-tumorale. Evaluarea unor potentiali biomarkeri care pot prezice sensibilitatea/raspunsul la tratament reprezinta un domeniu in plina expansiune in oncologie. Alaturi de biomarkeri, platformele omice si metodele biomedicale moderne reprezinta setul de instrumente necesar pentru consistenta, acuratetea si reproductibilitate datelor analizate. Dintre platformele proteomice, protein microarray ocupa o nisa specifica si importanta in descoperirea de biomarkeri, iar in ultima decada au fost dezvoltate si platforme dedicate diagnosticului. Populatiile celulare imune raman o sursa de biomarkeri ce trebuie corelati continuu cu terapiile actuale in cancer incluzand inhibitorii punctelor de control imun, anticorpi bispecifici sau vacinurile anti-tumorale. In cancerul cutanat, in special in melanomul malign, inalta heterogenitate tumorala si interactia complexa cu sistemul imun dicteaza combinarea metodelor de analiza, de la semnatura genica pana la fenotipul celular. Cum proteinele determina fenotipul, abordarea proteomica ofera posibilitatea de a masura efectele biologice cauzate de alterarile genomice. Biomarkerii solubili cum sunt citokinele si factorii de crestere (ex., MIF, IL-16, IL-10 etc) pot crea un micromediu inflamator care reprezinta o componenta consistenta a procesului malign. Alti factori „neconventionali” pentru seturile de markeri studiate in procesul tumoral (de ex., leptina) coreleaza axa imuna cu cea metabolica oferind suport potential pentru evaluarea efectelor terapiei. Astfel, studii recente releva faptula ca leptina – hormon crescut in obezitate, influenteaza direct functia limfocitelor T si implicit raspunsul la blocada axei PD-1. Elucidarea mecanismelor proceselor patologice este incompleta doar studiind peisajul genomic. Abordarile proteomice deceleaza alterarile proteice dar extind totodata corelatiile cu alte axe cheie din organism oferind date coroborate pentru caracterizarea de noi tinte terapeutice.
Lucrarea a fost finantata prin proiectele: PNIII-P1-1.2-PCCDI-2017-0341/2018 (acronim PATHDERM) si PN 19.29.01.01/2019.

Proteomics approaches for circulating biomarkers in skin cancer
Authors: Carolina Constantin, Mihaela Surcel, Ana Caruntu, Sabina Zurac, Monica Neagu

The immune backdrop in tumor process grasps a key role in antitumor therapy efficacy assessment. Evaluating certain potential biomarkers for therapy response prediction is nowadays an expanding domain. Besides biomarkers, omics methodologies and biomedical modern techniques are a robust tool mandatory for assuring data consistency, accuracy and reproducibility. Within proteomics platforms, protein microarray resides in a specific and important niche for biomarkers discovery, taking into account that in the last decade formats for diagnostic purposes has been also developed.
Immune cell populations are an invaluable biomarkers source that should be continuously correlated with actual therapeutic tendencies including immune checkpoint inhibitors, bi-specific antibodies and anti-tumor vaccines. In skin cancer, especially in cutaneous melanoma, high tumor heterogeneity and complex immune interactions claims combining analysis methods from genes signatures to cellular phenotype decoding. As proteins dictate phenotype fate, proteomic approaches would measure biological effects caused by genomic alterations. Soluble biomarkers such as cytokines or different growth factors (e.g., MIF, IL-6, IL-10 etc.) could generate an inflammatory milieu representing a steady component of neoplastic process. Other unconventional factors in relation to markers studied in tumor framework (e.g. leptin) could correlate immune and metabolic axis sustaining the tumor therapy efficacy assessment. Thus, recent data reveal that leptin, a hormone increased in obesity, directly influence T cells function and further PD-1 axis blockade response. Deciphering mechanisms underlying pathological processes would be insufficient only by genomic lens. Proteomic approaches detect protein alterations levels but also expand knowledge through important physiological axis to new therapeutic targets characterization.
Acknowledgment: study financed by PNIII-P1-1.2-PCCDI-2017-0341/2018 (acronym PATHDERM) and PN 19.29.01.01/2019 projects.

Scurt CV

Senior researcher I, PhD, biochemist, “Victor Babeș” National Institute of Pathology, Immunology Laboratory & Colentina Clinical Hospital, Research Core of Pathology Department, Bucharest.
Research topics: immune parameters analysis and biomarker discovery in melanoma and non-melanoma skin cancer; co-inventor for 4 patents related to photodynamic therapy PDT in skin pathologies. Dr. Constantin conducted national research projects related to novel photosensitizers for PDT in cancer, and drug-delivery nanosystems for skin regeneration; partner responsible for MNT_ERANET project 7030-1/2010 related to novel porphyrins in theranostics. Specialization in molecular biology at Ludwig Institute for Cancer Research, Signal Transduction Unit (Bruxelles); cellular biology specialization at University of Athens, Biochemistry and Physiology Department, in the frame of NATO SfP 982838/2007 project. Technical expert in 5 EU projects for biomedical assays; teaching experience in protein microarray technology; volunteer reviewer for several ISI journals.
Currently involved as MC member for COST Action CA18127 – International Nucleome Consortium (INC); MC substitute of the management committee for COST action CA16120 – European Epitranscriptomics Network (EPITRAN); alternate member of the management committee for CA18125 – Advanced Engineering and Research of Aerogels for Environment and Life Sciences (AEROGELS).