T cells cooperate in tumor killing as revealed by microfluidics and probabilistic modeling

Abstract

“Cytotoxic T cells are important components of natural anti-tumor immunity and are harnessed in tumor immunotherapies. Immune responses to tumors and immune therapy outcomes largely vary among individuals, but very few studies examine the contribution of intrinsic behavior of the T cells to this heterogeneity. Here we show the development of a microfluidic-based in vitro method to track the outcome of antigen-specific T cell activity on many individual cancer spheroids simultaneously at high spatiotemporal resolution, which we call Multiscale Immuno-Oncology on-Chip System (MIOCS). By combining parallel measurements of T cell behaviors and tumor fates with probabilistic modeling, we establish that the first recruited T cells initiate a positive feedback loop to accelerate further recruitment to the spheroid. We also provide evidence that cooperation between T cells on the spheroid during the killing phase facilitates tumor destruction. Thus, we propose that both T cell accumulation and killing function rely on collective behaviors rather than simply reflecting the sum of individual T cell activities, and the possibility to track many replicates of immune cell-tumor interactions with the level of detail our system provides may contribute to our understanding of immune response heterogeneity.”

“a Microfluidic chip on a standard glass slide. b Expanded view of the trapping region of the chip (dashed box) showing an array of 234 trapped droplets. Each droplet contains a single B16 spheroid in Matrigel, as shown in the inset. c Distribution of spheroid radii within a single chip (N = 215). d Viability measurements using live-dead staining after 24 and 48 h (N = 54). e Schematic showing a primary droplet with a tumor spheroid, followed by the addition and fusion of a secondary droplet containing GFP-labeled CTLs, eventually leading to tumor cell killing and spheroid fragmentation. Scale bar is 200 μm. f Schematic representation of the complete experimental protocol.” Reproduced under Creative Commons Attribution 4.0 International License from Ronteix, G., Jain, S., Angely, C. et al. High resolution microfluidic assay and probabilistic modeling reveal cooperation between T cells in tumor killing. Nat Commun 13, 3111 (2022).

Figures and the abstract are reproduced from Ronteix, G., Jain, S., Angely, C. et al. High resolution microfluidic assay and probabilistic modeling reveal cooperation between T cells in tumor killing. Nat Commun 13, 3111 (2022). https://doi.org/10.1038/s41467-022-30575-2 under Creative Commons Attribution 4.0 International License.

Read the original article: High resolution microfluidic assay and probabilistic modeling reveal cooperation between T cells in tumor killing

Pouriya Bayat