Publications

Authors:

De Sanctis, Francesco; Caligola, Simone; Anselmi, Cristina; Petrova, Varvara; Rossi, Barbara; Angelini, Gabriele; Erdeljan, Michael; Wöll, Stefan; Schlitter, Anna Melissa; Metzler, Thomas; Steiger, Katja; Borok, Zea; Bailey, Peter; Bauer, Aline; Halin, Cornelia; Boschi, Federico; Giugno, Rosalba; Canè, Stefania; Lawlor, Rita; Corbo, Vincenzo; Scarpa, Aldo; Constantin, Gabriela; Ugel, Stefano; Vascotto, Fulvia; Sahin, Ugur; Türeci, Özlem; Bronte, Vincenzo; Dusi, Silvia

Title:

Expression of the membrane tetraspanin claudin 18 on cancer cells promotes T lymphocyte infiltration and antitumor immunity in pancreatic cancer

Year:

2024

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Format:

Elettronico

Referee:

Sì

Name of journal:

Immunity

ISSN of journal:

1074-7613

N° Volume:

57

Number or Folder:

6

Page numbers:

1378-1393

Keyword:

claudin 18, pacreatic cancer, T lymphocytes; ALCAM; CD8(+) T lymphocytes; T lymphocyte infiltration; adhesion molecule; adoptive cell therapy; claudin 18; immunological synapse; pancreatic cancer; tumor microenvironment

Short description of contents:

Tumors weakly infiltrated by T lymphocytes poorly respond to immunotherapy. We aimed to unveil malig- nancy-associated programs regulating T cell entrance, arrest, and activation in the tumor environment. Dif- ferential expression of cell adhesion and tissue architecture programs, particularly the presence of the membrane tetraspanin claudin (CLDN)18 as a signature gene, demarcated immune-infiltrated from im- mune-depleted mouse pancreatic tumors. In human pancreatic ductal adenocarcinoma (PDAC) and non- small cell lung cancer, CLDN18 expression positively correlated with more differentiated histology and favor- able prognosis. CLDN18 on the cell surface promoted accrual of cytotoxic T lymphocytes (CTLs), facilitating direct CTL contacts with tumor cells by driving the mobilization of the adhesion protein ALCAM to the lipid rafts of the tumor cell membrane through actin. This process favored the formation of robust immunological synapses (ISs) between CTLs and CLDN18-positive cancer cells, resulting in increased T cell activation. Our data reveal an immune role for CLDN18 in orchestrating T cell infiltration and shaping the tumor immune contexture

Note:

Supplementary pages e1–e14 (STAR+METHODS)

Product ID:

139676

Handle IRIS:

11562/1126566

Last Modified:

July 10, 2024

Bibliographic citation:

De Sanctis, Francesco; Caligola, Simone; Anselmi, Cristina; Petrova, Varvara; Rossi, Barbara; Angelini, Gabriele; Erdeljan, Michael; Wöll, Stefan; Schlitter, Anna Melissa; Metzler, Thomas; Steiger, Katja; Borok, Zea; Bailey, Peter; Bauer, Aline; Halin, Cornelia; Boschi, Federico; Giugno, Rosalba; Canè, Stefania; Lawlor, Rita; Corbo, Vincenzo; Scarpa, Aldo; Constantin, Gabriela; Ugel, Stefano; Vascotto, Fulvia; Sahin, Ugur; Türeci, Özlem; Bronte, Vincenzo; Dusi, Silvia, Expression of the membrane tetraspanin claudin 18 on cancer cells promotes T lymphocyte infiltration and antitumor immunity in pancreatic cancer «Immunity» , vol. 57 , n. 6 , 2024 , pp. 1378-1393

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