Harder, better, faster, stronger: biochemistry and biophysics in the immunosurveillance concert

Abstract

Antitumor immunosurveillance is triggered by immune cell recognition of characteristic biochemical signals on the surfaces of cancer cells. Recent data suggest that the mechanical properties of cancer cells influence the strength of these signals, with physically harder target cells (more rigid) eliciting better, faster, and stronger cytotoxic responses against metastasis. Using analogies to a certain electronic music duo, we argue that the biophysical properties of cancer cells and their environment can adjust the volume and tone of the antitumor immune response. We also consider the potential influence of biomechanics-based immunosurveillance in disease progression and posit that targeting the biophysical properties of cancer cells in concert with their biochemical features could increase the efficacy of immunotherapy.

Figure 1.. Biophysics and biochemistry collaborate to make immunological music.

Cytotoxic lymphocyte activation by a tumor cell is schematized using the iconic Daft Punk pyramid. Biomechanical inputs, and force exertion though the filamentous actin cytoskeleton and cell surface integrins, are highlighted on the left, while key biochemical signaling pathways are highlighted on the right. Both components work in concert to elicit strong cytotoxic and inflammatory responses.

Key Figure, Figure 2.. The “Harder, better, faster, stronger” response of antitumor mechanosurveillance.

Schematic representing how “harder” metastatic cells that hyperactivate cytoskeletal pathways (pink with hatching) stimulate lymphocytes (blue) “better”, leading to “faster” cancer cell lysis and a “stronger” anti-tumor immune response compared with tumor cells that do not upregulate these activities (pink without hatching). Targeted molecules and immunotherapies, represented here as the Daft Punk duo, potentiate different aspects of the antitumor response. By acting together, they have the potential to enhance antitumor treatment synergistically.