# Vitamin D and Follicular Lymphoma

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2020 · $152,888

## Abstract

Program Director/Principal Investigator (Last, First, Middle): Friedberg, Jonathan, W
ABSTRACT
In addition to the primary effects on calcium homeostasis, Vitamin D has important effects on both
innate and adaptive immunity in humans. However, the degree to which these pleotropic effects of
Vitamin D influences specific immune responses to infections and cancer in humans is not known.
Indolent B-cell lymphoma represents a unique model system to define the effect of Vitamin D on the
immune response to cancer. Gene expression profiling studies demonstrate the importance of
immune-based signatures in the lymph node microenvironment on prognosis in follicular lymphoma. A
recently published study identified that immune-infiltration measured by PD-L2 expression in the
microenvironment of follicular lymphoma is strongly predictive of outcome, where low immune
infiltration was associated with increased risk of early relapse after initial therapy and ultimately
increased risk of death. As Vitamin D can upregulate tissue-specific PD-L1 and PD-L2 surface
glycoprotein expression in humans as a direct transcriptional inducer through the Vitamin D receptor,
Vitamin D may directly influence the immune response to malignancy. Our current R01 (CA214890)
funds a phase 3 clinical trial termed ILyAD (Indolent Lymphoma And Vitamin D), which randomizes
patients being treated with rituximab to Vitamin D supplementation with oral cholecalciferol 2000IU
daily, or placebo daily. At baseline and in follow-up, all patients have blood obtained for Vitamin D
levels, shipped to URMC labs on day of blood draw for central batched analysis using the gold standard
liquid chromatography-mass spectrometry (LCMS) method. Therefore, we have the unprecedented
opportunity to discover the direct relationship of Vitamin D treatment to immunomodulation in the setting
of indolent lymphoma. In this supplement, we propose to assess the tumor biopsies of patients in
ILyAD to assess immune infiltration, and correlate to baseline Vitamin D level. To evaluate specific cell
populations of interest, we will further characterize the immune infiltration patterns observed in tumors
from patients with low and high Vitamin D levels using spatial genomics. Leveraging the power of our
randomized, prospective trial, we will determine if Vitamin D supplementation can overcome the
negative prognosis of low immune infiltration on the trial. These assays therefore incorporate a
potential biomarker of response to Vitamin D, and providing important mechanistic insights around
Vitamin D with implications in other benign and malignant immune-reactive conditions.
OMB No. 0925-0001/0002 (Rev. 03/2020 Approved Through 02/28/2023) Page 1 Continuation Format Page

## Key facts

- **NIH application ID:** 10144553
- **Project number:** 3R01CA214890-04S1
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** JONATHAN W FRIEDBERG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $152,888
- **Award type:** 3
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10144553

## Citation

> US National Institutes of Health, RePORTER application 10144553, Vitamin D and Follicular Lymphoma (3R01CA214890-04S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10144553. Licensed CC0.

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