T028: Single-cell RNA sequencing reveals the interplay between circulating CD4 T cells, B cells and cancer-associated monocytes in classic Hodgkin lymphoma treated with PD-1 blockade Article Swipe
Julia Paczkowska
,
Ming Tang
,
Kyle Wright
,
Li Song
,
Vignesh Shanmugam
,
Kelsey Luu
,
Emma L. Welsh
,
Fathima Zumla Cader
,
Elisa Mandato
,
Jing Ouyang
,
Gali Bai
,
Lee N. Lawton
,
Scott J. Rodig
,
X. Shirley Liu
,
Margaret A. Shipp
·
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1097/01.hs9.0000890680.82329.6b
YOU?
·
· 2022
· Open Access
·
· DOI: https://doi.org/10.1097/01.hs9.0000890680.82329.6b
Classic Hodgkin lymphoma (cHL) is a largely MHC class I-negative tumor with recurrent 9p24.1/ PD-L1/ PD-L2 copy gains and the highest reported response rates to PD-1 blockade. In cHL, the efficacy of PD-1 blockade is closely associated with Hodgkin and Reed-Sternberg (HRS) cell expression of MHC class II, highlighting the potential role of CD4+ T-cell effectors and additional non-MHC class I-mediated mechanisms of tumor cell killing. We utilized scRNA sequencing to characterize the peripheral immune response to PD-1 blockade and more broadly define non-CD8+ dependent mechanisms of immune evasion in cHL. Peripheral blood mononuclear cells were obtained from 20 patients with relapsed/refractory (R/R) cHL treated with PD-1 blockade (nivolumab) on the CheckMate 205 clinical trial (cycle 1 day 1 [C1D1] and cycle 4 day 1 [C4D1]), 11 patients with newly diagnosed, previously untreated cHL and 13 healthy donors. Unlike healthy donors, all evaluated patients with cHL had circulating IFN stimulated adaptive and innate populations, including several distinct CD4+ T-cell effectors and an NK cell subset with reduced cytotoxic potential, and decreased numbers of B cells at all stages of differentiation. Patients with the most favorable responses to PD-1 blockade had: 1) significantly increased CD4+ T-cell receptor diversity and more abundant naïve/ central memory subsets; and 2) significantly higher B-cell receptor diversity and increased numbers of circulating B cells. The most abundant circulating CD3- population in patients with cHL was a newly identified monocyte subset with increased expression of multiple immunosuppressive and tumorigenic cytokines and chemokines, PD-L1 and SIRPa. This newly identified monocytic population was virtually absent from the blood of healthy donors. RNAscope analysis of the intact tumor microenvironment localized these tumor-infiltrating monocytes/macrophages to the immediate proximity of HRS cells. Monocytes from patients whose disease progressed following PD-1 blockade expressed significantly higher levels of immunosuppressive cytokine/chemokine signature which led to the development of a predictive transcriptional assay. We identified a comparable circulating monocyte population and transcriptional signature associated with unresponsiveness to PD-1 blockade in an additional solid tumor underscoring the broad-based significance of these findings.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1097/01.hs9.0000890680.82329.6b
- OA Status
- gold
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4303983602
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4303983602Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1097/01.hs9.0000890680.82329.6bDigital Object Identifier
- Title
-
T028: Single-cell RNA sequencing reveals the interplay between circulating CD4 T cells, B cells and cancer-associated monocytes in classic Hodgkin lymphoma treated with PD-1 blockadeWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2022Year of publication
- Publication date
-
2022-10-01Full publication date if available
- Authors
-
Julia Paczkowska, Ming Tang, Kyle Wright, Li Song, Vignesh Shanmugam, Kelsey Luu, Emma L. Welsh, Fathima Zumla Cader, Elisa Mandato, Jing Ouyang, Gali Bai, Lee N. Lawton, Scott J. Rodig, X. Shirley Liu, Margaret A. ShippList of authors in order
- Landing page
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https://doi.org/10.1097/01.hs9.0000890680.82329.6bPublisher landing page
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.1097/01.hs9.0000890680.82329.6bDirect OA link when available
- Concepts
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CD8, Immunology, Immune system, Biology, Cytotoxic T cell, Blockade, Peripheral blood mononuclear cell, T cell, MHC class I, Population, Cancer research, Medicine, Receptor, Genetics, In vitro, Environmental healthTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- Related works (count)
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10Other works algorithmically related by OpenAlex
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