Abstract
T cell-based tumor immunotherapies such as CAR T cells or immune checkpoint inhibitors harness the cytotoxic potential of T cells to promote tumor regression. However, patient response to immunotherapy remains heterogeneous, highlighting the need to better understand the rules governing a successful T cell attack. Here, we develop a microfluidic-based method to track the outcome of T cell activity on many individual cancer spheroids simultaneously, with a high spatiotemporal resolution. By combining these parallel measurements of T cell behaviors and tumor fate with probabilistic modeling, we establish that the first recruited T cells initiate a positive feedback loop leading to an accelerated effector accumulation on the spheroid. We also provide evidence that cooperation between T cells on the spheroid during the killing phase facilitates tumor destruction. We propose that tumor destruction does not simply reflect the sum of individual T cell activities but relies instead on collective behaviors promoting both T cell accumulation and function. The possibility to track many replicates of immune-tumor interactions with such a level of detail should help delineate the mechanisms and efficacy of various immunotherapeutic strategies.
Competing Interest Statement
CNB is inventor on several patents relating to the microfluidic technology. CNB is co-founder and scientific advisor to Okomera.