# Chemotherapy-induced MDSCs and antitumor immunity

> **NIH NIH R01** · AUGUSTA UNIVERSITY · 2021 · $347,700

## Abstract

Project Summary/Abstract
Recent advances in cancer immunotherapies have offered unprecedented opportunity to
harness the power of the immune system to fight against cancer. Some immunotherapies,
including adoptive T-cell therapy (ACT), are often preceded by chemotherapies which serve as
the frontline treatment and/or host pre-conditioning regimen. The impact of chemotherapy on
the efficacy of ACT is not fully understood. We previously reported that some anticancer drugs,
exemplified by cyclophosphamide (CTX), can drive the expansion of myeloid cells resembling
the well-studied myeloid-derived suppressor cells (MDSCs). These chemotherapy-induced
MDSCs, referred to as T-iMDSCs, are able to suppress T-cell responses. We have now
obtained evidence that T-iMDSCs can also induce stem-like cancer cells and enhance tumor
invasion. In addition, we found that CTX treatment induces DNA methyltransferase 1 (DNMT1),
and pharmacologically inactivating DNMT1 abrogates myeloid cell expansion after
chemotherapy. Based on these data, we propose that T-iMDSCs emerging after chemotherapy
promote the establishment of a tolerogenic tumor microenvironment (TME), which poses a
significant obstacle to the efficacy of adoptive T-cell therapy. Mechanistically, we hypothesize
that DNMT1 critically regulates post-chemotherapy hematopoietic recovery, giving rise to T-
iMDSCs with multifaceted tumor-promoting properties. The implication of this study is that
targeting T-iMDSCs relieves immunosuppression and sensitizes tumors to T cell therapy. The
significance of this proposal is that it reveals a previously overlooked tumor-promoting
mechanism inherent to chemotherapy. Our proposed studies will delineate the cellular and
molecular mechanisms governing the generation (Aim 1), define the tumor-promoting functions
of T-iMDSCs (Aim 2), establish effective strategies to target T-iMDSCs and potentiate ACT (Aim
3), and validate the presence of T-iMDSCs in patient samples. If successful, findings from this
project may guide the rational design of more effective chemo-immunotherapy regimens
capable of delivering durable and curative outcomes.

## Key facts

- **NIH application ID:** 10116304
- **Project number:** 5R01CA215523-05
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** GANG ZHOU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $347,700
- **Award type:** 5
- **Project period:** 2017-03-02 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10116304

## Citation

> US National Institutes of Health, RePORTER application 10116304, Chemotherapy-induced MDSCs and antitumor immunity (5R01CA215523-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10116304. Licensed CC0.

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