# Cancer-Associated Fibroblasts Alter the Composition of B cells in Solid Malignancies

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $356,850

## Abstract

Tumor stroma is increasingly recognized as an active participant in tumor progression. The two most
prominent stromal components in solid malignancies are immune cells and cancer-associated fibroblasts
(CAFs). Typically, the presence of immune cells is associated with favorable survival while the presence of
CAFs is associated with unfavorable survival. Although B-cell infiltrates are common in solid malignancies,
their contribution to survival has not been studied in detail. Both pro- and anti-tumor functions have been
demonstrated depending on the experimental system and markers used to detect B cells. The possibility that B
cells in different stages of differentiation have opposite effects on tumor progression has not been tested as
most prior studies used B-cell markers that detect a broad range of B-cell subsets. If certain subsets of B cells
are associated with tumor progression, we hypothesize that they will be enriched in metastases when
compared to primary tumors. Metastases typically have a higher content of CAFs than primary tumors. The
interdependence between B cells and CAFs has not been studied; however, it has recently been shown that
lymphoid organizer fibroblasts (LOFs) in normal lymph nodes regulate B cell recruitment to germinal centers
(GCs). We found that CAFs and LOFs share a common gene expression profile. This led us to hypothesize
that CAFs in solid tumors assume the function of LOFs to recruit and arrest B cells in the GC-stage of
development, thereby diminishing the production of functionally mature B cells. The proposed study will
characterize and quantitate the composition of B cells in matched primary and metastatic ovarian tumors using
combinations of markers that identify distinct stages of B-cell differentiation. The functional interdependence
between B cells and CAFs will be studied in co-cultures by quantitating the ability of CAFs to affect B-cell
recruitment, survival, and differentiation as well as the ability of B cells to potentiate pro-tumorigenic features of
CAFs. The interdependence between B cells and CAFs and its effect on tumor progression will be tested in
several genetically engineered mouse tumor models in which either subsets of B cells or CAFs are inactivated.
In addition to exploring a research area that has received limited attention in the past, the proposed study
addresses an urgent need for more effective immunotherapies. The success of B-cell therapies in hematologic
malignancies and autoimmune diseases and the emergence of new B-cell-directed agents have re-ignited
interest in B cells as therapeutic targets in solid tumors. However, a more detailed understanding of different B-
cell subsets and their roles in tumor growth are required for selective depletion of the tumor-promoting B-cell
subsets and/or control of their equilibrium in solid tumors. Our study will yield a quantitative map of individual
subsets of B-cells in matched primary tumors and metastases, clarify the potential role of...

## Key facts

- **NIH application ID:** 10213442
- **Project number:** 7R01CA208753-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** SANDRA ORSULIC
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $356,850
- **Award type:** 7
- **Project period:** 2020-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10213442

## Citation

> US National Institutes of Health, RePORTER application 10213442, Cancer-Associated Fibroblasts Alter the Composition of B cells in Solid Malignancies (7R01CA208753-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10213442. Licensed CC0.

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