# The immunosuppressive function of secretory IgM in tumor-bearing mice

> **NIH NIH K22** · METHODIST HOSPITAL RESEARCH INSTITUTE · 2021 · $194,184

## Abstract

Project Summary/Abstract
Myeloid-derived suppressor cells (MDSCs) exert potent immunosuppressive functions within tumor
microenvironments to promote tumor growth. It is critical to investigate the factors that can upregulate the
functions of MDSCs because such studies can potentially lead to new treatment strategies to suppress the
functions of MDSCs and reactivate the body's immune response to combat cancer. My published data generated
from several tumor mouse models strongly support that secretory IgM (sIgM) produced by normal and leukemic
B cells has strong immunosuppressive functions in inducing the accumulation and upregulating the functions of
MDSCs. To be able to translate my results into a potential therapeutic strategy, I decided to target the synthesis
of sIgM by deleting the function of XBP-1s, because the synthesis of sIgM is tightly regulated by a mechanism
called regulated IRE-1-dependent decay (RIDD), which is hyperactivated in B cells as a response to deficiency
of XBP-1s. Indeed, specific deletion of the XBP-1 gene in leukemic B cells and pharmacological inhibition of
XBP-1s in a B cell leukemia mouse model can lead to downregulated immunosuppressive functions of MDSCs,
supporting the therapeutic potential of targeting XBP-1s in inhibiting MDSCs. These data prompt me to identify
and characterize the mechanisms by which sIgM activates the immunosuppressive functions of MDSCs and to
investigate how to target sIgM to control MDSCs. My goals are summarized in the following Specific Aims: (1)
to identify and characterize the responsible receptors which mediate the immunosuppressive functions of sIgM;
(2) to investigate the downstream molecules that upregulate the immunosuppressive functions of MDSCs upon
stimulation by sIgM; and (3) to test whether deleting the function of XBP-1s from B cells can lead to reduced
growth of solid tumors via suppressing the production of sIgM.
Another main objective of this proposal is to help me initiate and maintain a successful independent research
group to conduct high quality research. To ensure successful completion of this objective, I have identified two
major areas that I will fortify: (1) to enhance my scientific progress through obtaining guidance from my advisory
committee/consultants/collaborators and attending scientific meetings; and (2) to facilitate my career
development through participating in workshops to improve my skills in grant writing, manuscript preparation,
oral presentation, and laboratory management. With protected time and stability provided by the K22 award, I
am confident that I can initiate my own independent research group and successfully compete for R01 funding.
My short-term goals are (1) to secure an independent faculty position; (2) to identify molecular mechanisms that
mediate immunosuppressive functions of sIgM; and (3) to establish new and close collaborations with colleagues
in my future institute. My long-term goals are (1) to develop ongoing projects based on ...

## Key facts

- **NIH application ID:** 9943704
- **Project number:** 1K22CA248354-01
- **Recipient organization:** METHODIST HOSPITAL RESEARCH INSTITUTE
- **Principal Investigator:** CHIH-HANG Anthony TANG
- **Activity code:** K22 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $194,184
- **Award type:** 1
- **Project period:** 2021-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9943704

## Citation

> US National Institutes of Health, RePORTER application 9943704, The immunosuppressive function of secretory IgM in tumor-bearing mice (1K22CA248354-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9943704. Licensed CC0.

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