ID

45605

Description

Principal Investigator: Hanlee Ji, MD, Stanford University School of Medicine, Palo Alto, USA MeSH: Lymphoma, Follicular,Lymphoma, Non-Hodgkin https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001378 Follicular lymphoma (FL) is a generally incurable B-cell malignancy which has the potential to transform into highly aggressive lymphomas. Genomic studies indicate it is often a small subpopulation rather than the dominant population in the FL that gives rise to the more aggressive subtype. To resolve the underlying transcriptional networks of follicular B-cell lymphomas at single molecule and cell resolution, we leveraged droplet-based barcoding technology for highly parallel single cell RNA-Seq. We analyzed the transcriptomes from tens of thousands of cells derived from five primary FL tumors. Simultaneously, we conducted multi-dimensional flow cell sorting to validate our characterizing of cellular lineages and critical expressed proteins. For each tumor, we identified multiple cellular subpopulations, matching known hematopoietic lineages. Comparison of gene expression by matched malignant and normal B cells from the same patient revealed tumor-specific features. Malignant B cells exhibited restricted immunoglobulin light chain expression (either Ig Kappa or Ig Lambda), as well the expected upregulation of the BCL2 gene, but also down-regulation of the FCER2, CD52 and MHC class II genes. By leveraging the single-cell resolution on large numbers of cells per patient, we were able to examine tumor-resident T cells. We identified pairs of immune checkpoint molecules that were co-expressed, providing a potentially useful strategy for selection of patient-tailored combination immunotherapies. In summary, massively parallel measurement of single-cell expression in thousands of tumor cells and tumor-resident lymphocytes can be used to obtain a systems-level view of the tumor microenvironment and identify new avenues for therapeutic development.

Link

dbGaP-study=phs001378

Keywords

  1. 2/19/23 2/19/23 - Chiara Middel
Copyright Holder

Hanlee Ji, MD, Stanford University School of Medicine, Palo Alto, USA

Uploaded on

February 19, 2023

DOI

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License

Creative Commons BY 4.0

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dbGaP phs001378 scRNA-Seq Reveals Lymphoma B Cell Diversity and T Cell Immune Checkpoint Co-Expression

Eligibility Criteria

Inclusion and exclusion criteria
Description

Inclusion and exclusion criteria

Alias
UMLS CUI [1,1]
C1512693
UMLS CUI [1,2]
C0680251
*Inclusion criteria for cases (lymphoma patients):*
Description

Elig.phs001378.v1.p1.1

Data type

boolean

Alias
UMLS CUI [1,1]
C1512693
UMLS CUI [1,2]
C0030705
UMLS CUI [1,3]
C0024299
>18 years of age
Description

Elig.phs001378.v1.p1.2

Data type

boolean

Alias
UMLS CUI [1,1]
C0001779
Diagnosis of non-Hodgkin's lymphoma or Hodgkin's disease, or any solid tumor, where standard of care procedure for tissue collection is planned (i.e. lymph node biopsy, FNA, core needle biopsy, skin punch biopsy, bone marrow biopsy, apheresis, splenectomy) and/or the patient has agreed to an additional biopsy or blood sample in addition to routine pathology
Description

Elig.phs001378.v1.p1.3

Data type

boolean

Alias
UMLS CUI [1,1]
C0011900
UMLS CUI [1,2]
C0024305
UMLS CUI [1,3]
C0019829
UMLS CUI [1,4]
C0280100
UMLS CUI [2,1]
C1301732
UMLS CUI [2,2]
C2936643
UMLS CUI [2,3]
C0199171
UMLS CUI [2,4]
C0200345
UMLS CUI [3,1]
C0030705
UMLS CUI [3,2]
C3641827
UMLS CUI [3,3]
C1524062
UMLS CUI [3,4]
C0005558
UMLS CUI [3,5]
C0005834
For lymphoma or solid tumor patients who do not have a diagnostic tumor tissue collection planned, availability of archival tumor tissue block or unstained slides.
Description

Elig.phs001378.v1.p1.4

Data type

boolean

Alias
UMLS CUI [1,1]
C1298908
UMLS CUI [1,2]
C1301732
UMLS CUI [1,3]
C2936643
UMLS CUI [1,4]
C0199171
UMLS CUI [1,5]
C0200345
UMLS CUI [1,6]
C0470187
UMLS CUI [1,7]
C0475358
Provide informed consent *Inclusion criteria for "healthy control" population:*
Description

Elig.phs001378.v1.p1.5

Data type

boolean

Alias
UMLS CUI [1,1]
C0021430
UMLS CUI [1,2]
C1512693
UMLS CUI [1,3]
C0009932
Diagnosis of non-cancer related surgical indication for lymph node(s) resection.
Description

Elig.phs001378.v1.p1.6

Data type

boolean

Alias
UMLS CUI [1,1]
C0011900
UMLS CUI [1,2]
C1298908
UMLS CUI [1,3]
C2826292
UMLS CUI [1,4]
C3146298
UMLS CUI [1,5]
C0543467
UMLS CUI [1,6]
C0024204
UMLS CUI [1,7]
C0728940
Provide informed consent *Exclusion criteria:*
Description

Elig.phs001378.v1.p1.7

Data type

boolean

Alias
UMLS CUI [1,1]
C0021430
UMLS CUI [1,2]
C0680251
not applicable
Description

Elig.phs001378.v1.p1.8

Data type

boolean

Alias
UMLS CUI [1,1]
C1272460

Similar models

Eligibility Criteria

Name
Type
Description | Question | Decode (Coded Value)
Data type
Alias
Item Group
Inclusion and exclusion criteria
C1512693 (UMLS CUI [1,1])
C0680251 (UMLS CUI [1,2])
Elig.phs001378.v1.p1.1
Item
*Inclusion criteria for cases (lymphoma patients):*
boolean
C1512693 (UMLS CUI [1,1])
C0030705 (UMLS CUI [1,2])
C0024299 (UMLS CUI [1,3])
Elig.phs001378.v1.p1.2
Item
>18 years of age
boolean
C0001779 (UMLS CUI [1,1])
Elig.phs001378.v1.p1.3
Item
Diagnosis of non-Hodgkin's lymphoma or Hodgkin's disease, or any solid tumor, where standard of care procedure for tissue collection is planned (i.e. lymph node biopsy, FNA, core needle biopsy, skin punch biopsy, bone marrow biopsy, apheresis, splenectomy) and/or the patient has agreed to an additional biopsy or blood sample in addition to routine pathology
boolean
C0011900 (UMLS CUI [1,1])
C0024305 (UMLS CUI [1,2])
C0019829 (UMLS CUI [1,3])
C0280100 (UMLS CUI [1,4])
C1301732 (UMLS CUI [2,1])
C2936643 (UMLS CUI [2,2])
C0199171 (UMLS CUI [2,3])
C0200345 (UMLS CUI [2,4])
C0030705 (UMLS CUI [3,1])
C3641827 (UMLS CUI [3,2])
C1524062 (UMLS CUI [3,3])
C0005558 (UMLS CUI [3,4])
C0005834 (UMLS CUI [3,5])
Elig.phs001378.v1.p1.4
Item
For lymphoma or solid tumor patients who do not have a diagnostic tumor tissue collection planned, availability of archival tumor tissue block or unstained slides.
boolean
C1298908 (UMLS CUI [1,1])
C1301732 (UMLS CUI [1,2])
C2936643 (UMLS CUI [1,3])
C0199171 (UMLS CUI [1,4])
C0200345 (UMLS CUI [1,5])
C0470187 (UMLS CUI [1,6])
C0475358 (UMLS CUI [1,7])
Elig.phs001378.v1.p1.5
Item
Provide informed consent *Inclusion criteria for "healthy control" population:*
boolean
C0021430 (UMLS CUI [1,1])
C1512693 (UMLS CUI [1,2])
C0009932 (UMLS CUI [1,3])
Elig.phs001378.v1.p1.6
Item
Diagnosis of non-cancer related surgical indication for lymph node(s) resection.
boolean
C0011900 (UMLS CUI [1,1])
C1298908 (UMLS CUI [1,2])
C2826292 (UMLS CUI [1,3])
C3146298 (UMLS CUI [1,4])
C0543467 (UMLS CUI [1,5])
C0024204 (UMLS CUI [1,6])
C0728940 (UMLS CUI [1,7])
Elig.phs001378.v1.p1.7
Item
Provide informed consent *Exclusion criteria:*
boolean
C0021430 (UMLS CUI [1,1])
C0680251 (UMLS CUI [1,2])
Elig.phs001378.v1.p1.8
Item
not applicable
boolean
C1272460 (UMLS CUI [1,1])

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