Immuno-oncology

The Tumor Suppressor APC Regulates T Lymphocytes Migration: Insights from Familial Polyposis Patients

Wednesday, June 22, 2022

3:45 PM – 4:00 PM PT

Location: Salons 5/6

Authors: Marta Mastrogiovanni, n/a (Presenting Author) - Institut Pasteur; Pablo Vargas, n/a (Co-Author) - Institut Curie; Thierry Rose, n/a (Co-Author) - Institut Pasteur; CÃ©line cuche, n/a (Co-Author) - Institut Pasteur; Marie Juzans, n/a (Co-Author) - Perelman School of Medicine University of Pennsylvania; Elric Esposito, n/a (Co-Author) - Institut Pasteur; Helene Laude, n/a (Co-Author) - Institut Pasteur; Charlotte Renaudat, n/a (Co-Author) - Institut Pasteur; Marie-Noelle Ungeheuer,, n/a (Co-Author) - Institut Pasteur; Jerome Delon, n/a (Co-Author) - Institut Cochin; Andres Alcover, n/a (Co-Author) - Institut Pasteur; Vincenzo Di Bartolo, n/a (Co-Author) - Institut Pasteur

Presenting Author(s)

MM

Marta Mastrogiovanni, n/a

Institut Pasteur
Paris, Ile-de-France, France

Co-Author(s)

PV

Pablo Vargas, n/a

Institut Curie
Paris, Ile-de-France, France
TR

Thierry Rose, n/a

Institut Pasteur
Paris, Ile-de-France, France
Cc

Céline cuche, n/a

Institut Pasteur
Paris, Ile-de-France, France
MJ

Marie Juzans, n/a

Perelman School of Medicine University of Pennsylvania
Philadelphia, Pennsylvania, United States
EE

Elric Esposito, n/a

Institut Pasteur
Paris, Ile-de-France, France
HL

Helene Laude, n/a

Institut Pasteur
Paris, Ile-de-France, France
CR

Charlotte Renaudat, n/a

Institut Pasteur
Paris, Ile-de-France, France
MU

Marie-Noelle Ungeheuer,, n/a

Institut Pasteur
Paris, Ile-de-France, France
JD

Jerome Delon, n/a

Institut Cochin
Paris, Ile-de-France, France
AA

Andres Alcover, n/a

Institut Pasteur
Paris, Ile-de-France, France
VD

Vincenzo Di Bartolo, n/a

Institut Pasteur
Paris, Ile-de-France, France

Chair(s)

Shachi Bhatt, PhD

Executive Editor
Journal of Experimental Medicine (JEM)

Abstract Text: Adenomatous polyposis coli (APC) is a tumor suppressor whose mutations underlie familial adenomatous polyposis (FAP) and colorectal cancer. While the importance of APC in epithelial homeostasis and its polarity regulator functions in non-immune cells are well established, its role in T cell biology and anti-tumor immunity remains poorly characterized.
APC regulates cytoskeleton organization, cell polarity and migration in various cells types. Appropriate migration of T cells and the ability to infiltrate tumors are required for efficient anti-tumor immune surveillance. Here we address whether APC plays a role in T lymphocyte migration, a key step of anti-tumor immune responses.
Using a series of cell biology tools, we unveiled that T cells from FAP patients carrying APC mutations display impaired adhesion and motility in constrained environments. We further dissected the cellular mechanisms underpinning these defects in APC-depleted CEM T cell line that recapitulate the phenotype observed in FAP T cells. We found that APC is critical not only for VLA-4-dependent adhesion but also for actomyosin and microtubule organization in migrating T cells. Finally, APC-silenced CEM cells preferentially adopt an ameboid-like migration featuring unstructured pseudopodia and blebbing.
These findings underscore a role of APC in T cell migration via modulation of integrin-dependent adhesion and cytoskeleton reorganization. Hence, APC mutations in FAP patients not only drive intestinal neoplasms, but also impair T cell migration, potentially leading to inefficient T cell-mediated anti-tumor immunity.