Decoding leukemia-immune cell dynamics by organism-wide cellular interaction mapping

Introduction

Cellular interactions are of fundamental importance in life, orchestrating organismal development, tissue homeostasis, and immunity. In the immune system, cell-cell interactions act as central hubs for information processing and decision making that collectively determine the outcome of complex immune responses.

Importance in Leukemias

In leukemias, a cancer originating from immature immune cells, a multilayered network of cellular interactions between immune and leukemic cells underlies effective immune control of the cancer, immune evasion, and response to immunotherapies. However, technical limitations in studying cell-cell interactions restrict our understanding of these highly complex and dynamic processes.

Proposed Approach

In order to overcome this limitation, I propose to develop a novel ‘interact-omics’ approach, capable of characterizing millions of cellular interactions across complex organ systems, entire organisms, and patient cohorts.

Application of the Approach

Applying the ‘interact-omics’ approach to sophisticated leukemia mouse models will enable us to:

1. Dissect the dynamic cellular interaction networks between antigen-specific T cells, bystander immune cells, and leukemic cells that drive anti-leukemia immunity and immune evasion.
2. In combination with the in vivo perturbation of cellular interactions, systematically decode the cellular logic of how the complex leukemia-immune interplay determines the disease course.

Understanding Therapy Resistance

Additionally, by making use of leukemia patient cohorts which are either responsive or non-responsive to immunotherapy treatment, we will:

1. Unravel previously unknown therapy resistance mechanisms.
2. Predict therapy response.

Conclusion

Together, our approach will set the basis for a comprehensive understanding of the leukemia-immune cell crosstalk underlying immune control, immune escape, and therapy response. It may serve as a blueprint to fundamentally expand our insights into other biological processes driven by cellular interactions.