Diatom-Based Artificial Antigen-Presenting Cells: A Novel Approach for Adaptive Immune Modulation

TL;DR

This paper introduces diatom-based artificial antigen-presenting cells that can modulate immune responses, offering a new approach for immunotherapy.

Contribution

The novel use of calcium-modified diatoms as artificial antigen-presenting cells for adaptive immune modulation is presented.

Findings

Amine polymerization on calcium-modified diatoms improved attachment of immunomodulatory proteins to the surface.

Diatom-based aAPCs promoted T cell activation markers and proliferation through costimulatory signaling.

Diatom-based aAPCs favored glycolysis over mitochondrial respiration to support immune activation.

Abstract

Artificial antigen-presenting cells (aAPCs) offer a precise
system
for modulating immune cells, effectively addressing major challenges
in immunotherapy, such as unintended effects. Diatoms have attracted
considerable interest as natural templates for biomaterials owing
to their surface characteristics, which can replicate those found
in cellular structures. In this study, we introduced the creation
of calcium-modified diatoms that act as artificial antigen-presenting
cells. This innovative strategy aims to enhance immunological interactions
and emulate the functions of natural antigen-presenting cells. Our
findings indicate that amine polymerization on calcium-modified diatoms
improved the attachment of immunomodulatory proteins (anti-CD28 and
anti-CD3) to the diatom surface, thereby promoting specific antibody–antigen
interactions with human T cells, as evidenced by the formation of
immunological synapses, which initiate targeted immune responses.
Through costimulatory signaling, we determined robust expression of
T cell activation markers, not only during early activation (CD69)
but also sustained at a later time point (CD25), associated with increased
T cell proliferation. Metabolically, diatom-based aAPCs promote glycolysis
over mitochondrial oxidative respiration to meet the elevated energy
demand for immune activation and homeostasis. Our findings suggest
that the immunofunctionalization of calcium-modified diatoms offers
a promising strategy for the development of bioinspired, functional
aAPC, which are adaptive immunomodulatory systems, and hold future
potential as immunotherapeutic platforms for diseases such as cancer
and autoimmunity.

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