# Spatially resolved, single cell biomarkers of B cell lymphoma

> **NIH NIH R01** · CEDARS-SINAI MEDICAL CENTER · 2022 · $616,249

## Abstract

Project Summary/Abstract
Diffuse Large B-Cell Lymphoma (DLBCL) is the most common form of Non-Hodgkin Lymphoma (NHL). DLBCL
tumors are highly heterogeneous and molecular profiling has revealed up to six distinct prognostically relevant
sub-groups, however these classifications are primarily based on profiles of the malignant cells. Non-malignant
cells in the tumor immune microenvironment (TME) can be powerful modulators of tumor growth and can be
targeted for cancer therapy, yet biomarkers that include TME elements have not been developed. We
hypothesize that successful development of next generation immune targeting therapies for lymphoma
will require spatially resolved, highly multiplexed single cell based biomarkers of TME composition and
structure. In this study we propose to perform imaging mass cytometry analysis (IMC) on over 2000 cases of
aggressive B cell lymphoma with the following aims: Specific Aim 1: Validate spatially-derived protein biomarkers
of DLBCL outcomes (n-830 patients). Specific Aim 2: Analyze the single cell topology of histologically diverse
aggressive B cell lymphomas (n=1380) to identify shared TME based biomarkers across all aggressive B cell
lymphoma. Specific Aim 3: Determine which TME elements modulate chemoresistance and mediate response
to immune therapies in lymphoma through in vitro model systems. In the first two Aims, we will apply our novel
abundance weighted score (M-score), developed specifically for IMC analysis, to validate candidate biomarkers
(such as PD-L1+/CCR4+/TIM-3+) and identify new biomarkers. We will also apply our single cell spatial
clustering algorithm, Regions of Immune Cell Organization (RICO), to identify tumor-immune spatial clusters
that are associated with clinical outcome. The spatial resolved, single cell, highly multiplexed, digital image
analysis proposed here will have clinical impact for the ~80,000 new US cases of NHL. Specific Aim 1 will validate
and discover protein biomarkers in a image format familiar to pathologists allowing for seamless clinical
adoption, Specific Aim 2 will refine methods for spatial systems biology applied to challenging lymphoma
types, and Specific Aim 3 will allow pre-clinical validation of prognostic and predictive biomarkers.

## Key facts

- **NIH application ID:** 10522993
- **Project number:** 1R01CA266544-01A1
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** Akil Merchant
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $616,249
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10522993

## Citation

> US National Institutes of Health, RePORTER application 10522993, Spatially resolved, single cell biomarkers of B cell lymphoma (1R01CA266544-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10522993. Licensed CC0.

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