posted on 2021-03-22, 11:38authored byManola Moretti, Rosanna La Rocca, Michela Perrone Donnorso, Bruno Torre, Claudio Canale, Mario Malerba, Gobind Das, Rosa Sottile, Cinzia Garofalo, Adnane Achour, Klas Kärre, Ennio Carbone, Enzo Di Fabrizio
The activation of the T cell mediated
immune response relies on
the fine interaction between the T cell receptor on the immune cell
and the antigen-presenting major histocompatibility complex (MHC)
molecules on the membrane surface of antigen-presenting cells. Both
the distribution and quantity of MHC/peptide complexes and their adequate
morphological presentation affect the activation of the immune cells.
In several types of cancer the immune response is down-regulated due
to the low expression of MHC-class I (MHC-I) molecules on the cell’s
surface, and in addition, the mechanical properties of the membrane
seem to play a role. Herein, we investigate the distribution of MHC-I
molecules and the related nanoscale mechanical environment on the
cell surface of two cell lines derived from colon adenocarcinoma and
a healthy epithelial colon reference cell line. Atomic force microscopy
(AFM) force spectroscopy analysis using an antibody-tagged pyramidal
probe specific for MHC-I molecules and a formula that relates the
elasticity of the cell to the energy of adhesion revealed the different
population distributions of MHC-I molecules in healthy cells compared
to cancer cells. We found that MHC-I molecules are significantly less
expressed in cancer cells. Moreover, the local elastic modulus is
significantly reduced in cancer cells. We speculate that these results
might be related to the proven ability of cancer cells to evade the
immune system, not only by reducing MHC-I cell surface expression
but also by modifying the local mechanical properties affecting the
overall morphology of MHC-I synapse presentation to immune cells.