Tumor cell spheroid-induced suppression of primary human cytotoxic T cells as a scalable <i>in vitro</i> model of exhaustion.

ABSTRACT:

Background

Cytotoxic T lymphocytes (CTL) are key effectors in the antitumor immune response. However, their function is commonly suppressed in tumors in the form of exhausted CTL. Understanding mechanisms of suppression and of therapeutics to overcome them is of substantial basic and translational importance yet hindered by limited access to large numbers of exhausted CTL in vitro.

Methods

Here we use three-dimensional tissue culture to generate primary human CTL with suppressed function. Using functional assays, a 21-antibody flow cytometry panel and determination of calcium signaling and CTL tumor cell couple maintenance, we have characterized their phenotype.

Results

We show that these cells closely resemble exhausted CTL from tumors. For a better understanding of

SUBMITTER: Alsubaiti A 

PROVIDER: S-EPMC12207883 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature