# The regulation of dendritic cell function by LMYC at steady state and during immune responses to cancer

> **NIH NIH F31** · WASHINGTON UNIVERSITY · 2020 · $31,438

## Abstract

Project Summary
 It is estimated that nearly 1.5 million new cases of cancer are reported each year. Until recently,
treatment options for metastatic cancers have been limited. However, therapies that harness the activity of the
host immune system have proven successful in the treatment of recalcitrant cancers such as melanoma, acute
lymphoblastic leukemia and Hodgkin lymphoma. Numerous immune cell lineages regulate anti-tumor
responses, including Batf3-dependent dendritic cells, which cross-present antigens to naïve CD8 T cells and
initiate adaptive immune responses against cancer cells. Therefore, research to identify the factors that
regulate the development and function of dendritic cells can advance our understanding of immune responses
to cancer and reveal putative molecular targets for cancer immunotherapy.
 The present proposal aims to define the mechanism by which the transcription factor, LMYC, regulates
DC function and in turn whether LMYC is required for steady state and immunotherapy-induced tumor
rejection. We have generated Mycl1-GFP knockin/knockout mice that serve as in vivo reporters of Mycl1
expression and Mycl1-deficiency. Using this model, we have shown previously that Mycl1 is required for
optimal priming of naïve CD8 T cells during infections. Given that both CD8 T cells and Batf3-dependent
dendritic cells are required for tumor rejection and positive responses to immunotherapy, we hypothesize that
Mycl1 is required for these processes. In Aim1, we will define the molecular mechanism by which LMYC
supports the core function of Batf3-dependent dendritic cells. We will first determine the impact of LMYC
deficiency on global transcription to identify pathways that are dysregulated at steady state. In vivo and in vitro
biochemical analyses will be employed to validate that broad defects in transcription result in downstream
effects on core biological processes, such as protein synthesis and respiration, which are broadly regulated by
MYC family members. In Aim2, we will determine whether steady state and immunotherapy-induced rejection
of immunogenic tumors is dependent on intrinsic expression of Mycl1 by Batf3-dependent dendritic cells.
Simultaneously, we will analyze the impact of the tumor microenvironment and immunotherapies on the
expression of Mycl1 by dendritic cells in vivo. If Mycl1 expression correlates with rejection outcomes in a
mouse model of checkpoint blockade, it may serve as a molecular biomarker to predict patient responses to
cancer immunotherapy. Therefore, the results of this study will advance our understanding of the molecular
mechanisms that control dendritic cell function as well as the molecules required for steady state and
immunotherapy-induced immune responses to cancer.

## Key facts

- **NIH application ID:** 9900755
- **Project number:** 5F31CA228240-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** David Alexander Anderson
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $31,438
- **Award type:** 5
- **Project period:** 2018-04-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900755

## Citation

> US National Institutes of Health, RePORTER application 9900755, The regulation of dendritic cell function by LMYC at steady state and during immune responses to cancer (5F31CA228240-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9900755. Licensed CC0.

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