bims-actimu 2023-10-29 papers

Issue of 2023–10–29
two papers selected by
Elodie Busch, University of Strasbourg

bioRxiv. 2023 Oct 04. pii: 2023.10.02.560434. [Epub ahead of print]

WASP facilitates tumor mechanosensitivity in T lymphocytes.

Srishti Mandal, Mariane Melo, Pavlo Gordiichuk, Sayanti Acharya, Yeh-Chuin Poh, Na Li, Aereas Aung, Eric L Dane, Darrell J Irvine, Sudha Kumari.

Cytotoxic T lymphocytes (CTLs) carry out immunosurveillance by scanning target cells of diverse physical properties for the presence of antigens. While the recognition of cognate antigen by the T cell receptor is the primary signal for CTL activation, it has become increasingly clear that the mechanical stiffness of target cells plays an important role in antigen-triggered T cell responses. However, the molecular machinery within CTLs that transduces the mechanical information of tumor cells remains unclear. We find that CTL's mechanosensitive ability requires the activity of the actin-organizing protein Wiskott-Aldrich Syndrome Protein (WASP). WASP activation is modulated by the mechanical properties of antigen-presenting contexts across a wide range of target cell stiffnesses and activated WASP then mediates mechanosensitive activation of early TCR signaling markers in the CTL. Our results provide a molecular link between antigen mechanosensing and CTL immune response and suggest that CTL-intrinsic cytoskeletal organizing principles enable the processing of mechanical information from diverse target cells.

DOI: https://doi.org/10.1101/2023.10.02.560434

Front Immunol. 2023 ;14 1276602

Actin cytoskeleton remodeling at the cancer cell side of the immunological synapse: good, bad, or both?

Elena Ockfen, Liza Filali, Diogo Pereira Fernandes, Céline Hoffmann, Clément Thomas.

Cytotoxic lymphocytes (CLs), specifically cytotoxic T lymphocytes and natural killer cells, are indispensable guardians of the immune system and orchestrate the recognition and elimination of cancer cells. Upon encountering a cancer cell, CLs establish a specialized cellular junction, known as the immunological synapse that stands as a pivotal determinant for effective cell killing. Extensive research has focused on the presynaptic side of the immunological synapse and elucidated the multiple functions of the CL actin cytoskeleton in synapse formation, organization, regulatory signaling, and lytic activity. In contrast, the postsynaptic (cancer cell) counterpart has remained relatively unexplored. Nevertheless, both indirect and direct evidence has begun to illuminate the significant and profound consequences of cytoskeletal changes within cancer cells on the outcome of the lytic immunological synapse. Here, we explore the understudied role of the cancer cell actin cytoskeleton in modulating the immune response within the immunological synapse. We shed light on the intricate interplay between actin dynamics and the evasion mechanisms employed by cancer cells, thus providing potential routes for future research and envisioning therapeutic interventions targeting the postsynaptic side of the immunological synapse in the realm of cancer immunotherapy. This review article highlights the importance of actin dynamics within the immunological synapse between cytotoxic lymphocytes and cancer cells focusing on the less-explored postsynaptic side of the synapse. It presents emerging evidence that actin dynamics in cancer cells can critically influence the outcome of cytotoxic lymphocyte interactions with cancer cells.

Keywords: actin cytoskeleton; cancer; cytotoxic T cells; cytotoxic lymphocytes; immunological synapse; natural killer cells

DOI: https://doi.org/10.3389/fimmu.2023.1276602