Systems immunology: Collective behavior in immune triads(ongoing)

The immune system is often described in terms of individual cells and molecules, but many of its most important behaviors emerge only at the collective level. In cancer, effective immune responses appear to depend not simply on the presence of the right cells, but on whether those cells assemble into the right local structures and communicate in the right way. This raises a deeper question: what are the rules that allow immune cells to act as a coordinated multicellular system rather than as isolated parts?

This work explores this question by focusing on how spatial organization, local composition, and cell–cell communication shape collective immune behavior. I am particularly interested in whether there are specific geometric and population-level conditions under which immune cells become functionally coordinated, and whether these conditions can be engineered and measured in controlled experimental systems. Rather than treating immunity only as a molecular signaling problem, this approach asks whether tissue-scale function can be understood from the logic of small interacting groups.

More broadly, this research sits at the intersection of systems biology, immunology, and engineered microenvironments. The goal is not only to describe immune coordination, but to uncover quantitative principles that could eventually help us predict and steer it. By combining controlled multicellular experiments with computational thinking, I aim to better understand how collective immune behavior emerges—and when it fails.

Read More:

References:

1. Cheng, K. et al. Spatial interactions of immune cells as potential predictors to efficacy of toripalimab plus chemotherapy in locally advanced or metastatic pancreatic ductal adenocarcinoma: a phase Ib/II trial. Signal Transduct. Target. Ther. 9, 321 (2024).
2. Forlin, R., James, A. & Brodin, P. Making human immune systems more interpretable through systems immunology. Trends Immunol. 44, 577–584 (2023).
3. Espinosa-Carrasco, G. et al. Intratumoral immune triads are required for immunotherapy-mediated elimination of solid tumors. Cancer Cell 42, 1202-1216.e8 (2024).
4. Tewary, M. et al. High-throughput micropatterning platform reveals Nodal-dependent bisection of peri- gastrulation–associated versus preneurulation-associated fate patterning. PLOS Biol. 17, e3000081 (2019).
5. Alon, U. Network motifs: theory and experimental approaches. Nat. Rev. Genet. 8, 450–461 (2007).
6. Shen, K., Thomas, V. K., Dustin, M. L. & Kam, L. C. Micropatterning of costimulatory ligands enhances CD4+ T cell function. Proc. Natl. Acad. Sci. 105, 7791–7796 (2008).
7. Sadoun, A. et al. Controlling T cells spreading, mechanics and activation by micropatterning. Sci. Rep. 11, 6783 (2021).
8. Stybayeva, G. et al. Micropatterned co-cultures of T-lymphocytes and epithelial cells as a model of mucosal immune system. Biochem. Biophys. Res. Commun. 380, 575–580 (2009).
9. Achar, S. R. et al. Universal antigen encoding of T cell activation from high-dimensional cytokine dynamics. Science (2022) doi:10.1126/science.abl5311.
10. Heydari, T. et al. IQCELL: A platform for predicting the effect of gene perturbations on developmental trajectories using single-cell RNA-seq data. PLOS Comput. Biol. 18, e1009907 (2022).