Objective: The rationale for the proposed research is the need to better understand the extent to which cancer populations adopt active immune evasion strategies to evade T cell recognition in the setting of allogeneic CD8+ T cell immunotherapy. We currently lack a theoretical framework for cancer T cell evasion.

Therefore, the objective of this research is to develop a mathematical model to quantify the degree to which cancer populations employ adaptive, immune-specific evasion strategies, to apply this model to experimental data detailing cancer immune recognition and evasion, and to propose model-predicted, optimized hematopoietic stem cell transplant (HSCT) strategies in the setting of a...

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Objective: The rationale for the proposed research is the need to better understand the extent to which cancer populations adopt active immune evasion strategies to evade T cell recognition in the setting of allogeneic CD8+ T cell immunotherapy. We currently lack a theoretical framework for cancer T cell evasion.

Therefore, the objective of this research is to develop a mathematical model to quantify the degree to which cancer populations employ adaptive, immune-specific evasion strategies, to apply this model to experimental data detailing cancer immune recognition and evasion, and to propose model-predicted, optimized hematopoietic stem cell transplant (HSCT) strategies in the setting of acute myeloid leukemia (AML).

Goals: The proposed project will be investigated by studying three specific aims. In Specific Aim 1, the goal is to develop a mathematical model capable of quantifying the differences in cancer dynamics resulting from variability in the aggressiveness of the cancer immune-specific evasion strategy. In Specific Aim 2, the first goal is to relate chromatin structural data to tumor antigen (TA) availability, and therefore cancer immunogenicity. The second goal is to apply our model on TCR sequencing and cancer deep sequencing data for AML patients to assess the extent of experimentally observed immune evasion. Lastly, the primary goal in Specific Aim 3 is to use our model on AML patient time course data to recapitulate known outcome, and then to use our specificity model to identify donor immune systems predicted to generate improved patient outcome.

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