# Microbiota and the anti-tumor action of anti-CD47 immunomodulation.

> **NIH NIH R21** · UNIVERSITY OF CHICAGO · 2020 · $211,410

## Abstract

Project Summary: The commensal microbiota plays a prominent role in the regulation of immunity. Due to
recent advances in our understanding of mechanisms underlying the efficacy of cancer therapies, the gut
microbiota has been implicated in modulating the efficacy of various immunotherapies. Tumor cell expression
of CD47, a transmembrane protein signaling “don’t eat me” to phagocytes, promotes immune evasion and
tumor relapse. Notably, differential anti-CD47 antibody-induced tumor control has been observed, and our
preliminary data indicate that different commensal microbiota produce different anti-tumor responses to CD47
blockade: 1) Tumor-bearing wild-type (WT) mice from Jackson Labs (Jax) responded better to CD47 blockade
immunotherapy compared with tumor-bearing mice from Taconic Farms (Tac); 2) antibiotic feeding eliminated
the anti-tumor responses in WT mice from Jax; 3) after cohousing with Jax mice, tumor control was enhanced
in Tac mice following CD47 blockade; 4) anti-tumor effects were not detected in Germ-Free (GF) WT mice
after CD47 blockade; and 5) differences in anti-CD47-induced tumor control were transferred through oral
gavage of fecal microbiota.
HYPOTHESIS: We hypothesize that the gut microbiota modulate anti-tumor immune responses elicited by CD47
blockade, which could explain the previously observed differential therapeutic responses.
Aim 1: Investigate the cellular and molecular mechanisms related to how gut microbiota govern anti-
tumor effects induced by anti-CD47 antibody treatment.
Aim 2: Identification of microbiota species that mediate antitumor immunity after CD47 blockade.
TRANSFORMATIVE POTENTIAL: Checkpoint inhibitors have transformed the treatment of human cancers such as
malignant melanoma and lung cancer; however, these nascent immunomodulatory approaches have proven
effective thus far in only a subset of patients. While limited preclinical and clinical data suggest that probiotic
treatment can promote a gut microbiome that is amenable to the antitumor effects of immunotherapies and
chemotherapies, the status and effects of commensal microbiota are currently not widely considered as part
of standard practice, even though many cancer patients currently receive pro- and/or antibiotics prior to or
during the course of their treatment, for indications such as treatment toxicity and infection. This study has the
potential to change clinical practice: determination of the presence or absence of microbiota that potentiates
CD47 blockade could improve anti-tumor effects, and expand the patient population that responds to this
immune checkpoint inhibitor currently in clinical trials. !

## Key facts

- **NIH application ID:** 9989818
- **Project number:** 5R21CA231273-02
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** RALPH R WEICHSELBAUM
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $211,410
- **Award type:** 5
- **Project period:** 2019-08-06 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989818

## Citation

> US National Institutes of Health, RePORTER application 9989818, Microbiota and the anti-tumor action of anti-CD47 immunomodulation. (5R21CA231273-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9989818. Licensed CC0.

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