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.

Technical Limitations

However, technical limitations in studying cell-cell interactions restrict our understanding of these highly complex and dynamic processes.

Proposed Solution

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 dissect the dynamic cellular interaction networks between:

1. Antigen-specific T cells
2. Bystander immune cells
3. Leukemic cells

These interactions drive anti-leukemia immunity and immune evasion.

In Vivo Perturbation

In combination with the in vivo perturbation of cellular interactions, this will allow us to 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 that are either responsive or non-responsive to immunotherapy treatment, we will unravel previously unknown therapy resistance mechanisms and 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.