Jonathan Nowak, Molecular and Gastrointestinal Pathologist at Brigham and Women’s Hospital and the Dana-Farber Cancer Institute, shared on LinkedIn:
“New paper out in Cancer Discovery!
Proud to share our latest work from the Dana-Farber Cancer Institute GI Cancer Center and Wolpin-Nowak lab:
‘Impact of vitamin D on the colon cancer immune microenvironment: results of a randomized clinical trial of preoperative vitamin D supplementation in patients with stage I-III colon cancer.’
We paired pre-treatment biopsies with post-treatment surgical resections and used custom multiplex immunofluorescence assays and spatial whole-transcriptome profiling to trace, cell by cell and region by region, how vitamin D reshapes colon cancer and its immune microenvironment.
Here’s what we found in an analysis led by pathologist Andressa Dias Costa in a DFCI/BWH-based clinical trial conceived and run by GI medical oncologist Kimmie Ng.
- Vitamin D supplementation significantly increased plasma 25-hydroxyvitamin D levels
- Vitamin D receptor (VDR) expression was highly heterogeneous across tumor, immune, and stromal compartments, underscoring the importance of dissecting vitamin D effects on multiple cell types in the tumor microenvironment
- VDR expression localized preferentially to the tumor invasive front in vitamin D-treated patients, whereas an opposite pattern was seen with placebo treatment
- Vitamin D supplementation increased memory CD3+CD8+ T cell density and reduced regulatory CD3+CD8+FOXP3+ T cell density in resected tumors, and also resulted in greater co-localization of CD8+ T cells with tumor cells
- VDR functions primary as a transcriptional repressor in CRC epithelial cells
- Vitamin D supplementation is associated with changes in epithelial differentiation and barrier integrity as well as inflammatory responses and mucosal defense
Together, the data point to a real, measurable anti-tumor immune effect of vitamin D in the colon cancer microenvironment and open the door to further mechanistic work on how to harness it.
These results build on our group’s longstanding interest in vitamin D as a modulator of tumor behavior and anti-tumor immunity across GI cancers.
Grateful to our co-authors and, most of all, to the patients whose participation made this trial possible.”
Title: Impact of vitamin D on the colon cancer immune microenvironment: results of a randomized clinical trial of preoperative vitamin D supplementation in patients with stage I-III colon cancer
Authors: Andressa Dias Costa, Suryun Kim, Sung Chul Hong, Chen Yuan, Xinran Qi, Jinming Zhang, Ronald Bleday, Joel Goldberg, Jennifer Irani, Nelya Melnitchouk, Ewa T. Sicinska, Kristen E. Lowder, Jennifer S. Thalappillil, Yasutoshi Takashima, Sara A. Väyrynen, Elizabeth M. Payne, Jeffrey A. Meyerhardt, Matthew B. Yurgelun, Thomas A. Abrams, Emma C. Coleman, Bridget Fitzpatrick, Christine Ganser, Katherine A. Metayer, Lauren K. Brais, Ramesh A. Shivdasani, Brian M. Wolpin, Bruce W. Hollis, Jonathan A. Nowak, Kimmie Ng
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