Shaping innate lymphoid cell infiltration of colorectal cancer metastasis by targeting chemokine receptors

Anno
2020
Proponente Giovanni Bernardini - Professore Associato
Sottosettore ERC del proponente del progetto
LS6_1
Componenti gruppo di ricerca
Componente Categoria
Cristina Cerboni Componenti strutturati del gruppo di ricerca / Structured participants in the research project
Maria Helena Stabile Componenti strutturati del gruppo di ricerca / Structured participants in the research project
Giuseppe Sciume' Componenti strutturati del gruppo di ricerca / Structured participants in the research project
Silvano Sozzani Componenti strutturati del gruppo di ricerca / Structured participants in the research project
Andrea Kosta Dottorando/Assegnista/Specializzando componente non strutturato del gruppo di ricerca / PhD/Assegnista/Specializzando member non structured of the research group
Luisa Loconte Dottorando/Assegnista/Specializzando componente non strutturato del gruppo di ricerca / PhD/Assegnista/Specializzando member non structured of the research group
Rosa Molfetta Componenti strutturati del gruppo di ricerca / Structured participants in the research project
Luana Tomaipitinca Dottorando/Assegnista/Specializzando componente non strutturato del gruppo di ricerca / PhD/Assegnista/Specializzando member non structured of the research group
Componente Qualifica Struttura Categoria
Mazej Julija borsista Marie-Curie (MSCA-ITN) Dipartimento Medicina Molecolare Altro personale aggregato Sapienza o esterni, titolari di borse di studio di ricerca / Other aggregate personnel Sapienza or other institution, holders of research scholarships
Abstract

Immunotherapy represents a promising approach for cancer treatment but is frequently ineffective due to immune escape mechanisms or ineffective tumor leukocyte infiltration. To further extent the remarkable success of tumor immunotherapy, a better understanding of the mechanisms that regulate immune cell recruitment and function in the tumor microenvironment is required. Metastatic colorectal cancer (CRC) is one of the main causes of death associated with tumors. Myeloid cells play an important role in CRC carcinogenesis and progression due to release of factors that promote tumor growth and suppress the immune response. Indeed, elmination of myeloid cells, or blockade of their tissue recruitment reduce tumor incidence and the ability to form liver metastases in CRC mouse models. Accumulating evidence suggests that myeloid cells inhibit NK cell anti-tumor activity, thus limiting cancer immune surveillance. Correspondingly, we found that CRC liver metastasis are associated with the expansion of lymphoid cells resembling a recentlly described NK cell-derived population of intILC1 with pro-tumoral function.
The chemokine system has a central role in orchestrating the immune response in tumor determining extravasation to primary tumor and to metastatic sites and activation of anti-tumor potential. The main objective of the present proposal is to improve the anti-tumor immune response by inhibiton of myeloid cell tumor infiltration in combination with strategies that promote of NK cell-mediated effector functions. Thus we will i) identify myeloid cell populations with NK/ILC1 suppressive activity that expand in CRC liver metastasis ii) inhibit their tissue recruitment by chemokine receptor targeting; iii) clarify the molecular basis and effects of innate lymphoid cell plasticity and mechanisms of recruitment in CRC metastasis; iv) identify new potential strategies of immunotherapies, by manipulation of the chemokine system to unleash the anti-tumor activity of NK/ILC1.

ERC
LS6_1, LS6_3, LS6_4
Keywords:
IMMUNITA¿ INNATA, CANCRO, DIFFERENZIAMENTO, FISIOLOGIA E DINAMICA CELLULARE

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