# Targetable Immune Evasion Pathways in Hodgkin Lymphoma

> **NIH NIH R01** · DANA-FARBER CANCER INST · 2020 · $373,399

## Abstract

Project Summary
Our current approaches to the diagnosis and treatment of lymphoid malignancies do not reflect emerging data
regarding pathogenetic mechanisms and associated rational treatment targets. For example, one of the main
lymphoid malignancies to strike young and otherwise healthy adults, classical Hodgkin lymphoma (cHL), is
largely defined by its morphologic appearance and treated with an empiric combination of available
chemotherapeutic agents. We previously hypothesized that 9p24.1/PD-L1/PD-L2 copy number alteration
(CNA) was a genetic mechanism of immune evasion in cHL and considered the PD-1 pathway to be a rational
therapeutic target in this disease. After defining recurrent 9p24.1 copy gain and increased PD-L1/PD-L2
expression as high-frequency events in cHL, we explored the clinical activity of PD-1 blockade in this lymphoid
malignancy. In independent pilot studies of two different PD-1 blocking agents, patients with multiply
relapsed/refractory cHL experienced remarkable clinical responses that were often durable. In our competitive
renewal application, we propose to build on these findings with the following specific aims: 1.0) Determine the
relationship between PD-L1/PD-L2 alterations and outcome, response to PD-1 blockade and additional genetic
bases of immune evasion in cHL; 2.0) Elucidate mechanisms of response and resistance to PD-1 blockade in
cHL patients; 3.0) Develop a comprehensive approach to analyze genetic bases for immune evasion in cHL;
and 4.0) Define the clinical activity of PD-1 blockade at earlier timepoints in the treatment of cHL. The
proposed studies, will define complementary and/or confounding genetic bases of immune evasion and
mechanisms of response and resistance to PD-1 blockade and inform our incorporation of PD-1 blockade into
the standard therapy of cHL.

## Key facts

- **NIH application ID:** 9963148
- **Project number:** 5R01CA161026-10
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Margaret A Shipp
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $373,399
- **Award type:** 5
- **Project period:** 2011-08-22 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9963148

## Citation

> US National Institutes of Health, RePORTER application 9963148, Targetable Immune Evasion Pathways in Hodgkin Lymphoma (5R01CA161026-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9963148. Licensed CC0.

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