Table 6.

Clinical significance of scRNA-seq in various lymphoma

Malignancies	Year	Species	Protocol	Accession number (custom database if available)	Clinical significance	References
Diffuse large B cell lymphoma	2019	Mouse	Smart-seq2	Correspondence with authors	Identified a “superphagocytic” macrophage subset that expressed CD36/FCGR4, and defined a novel mechanism through which high-dose alkylating agents promote macrophage-dependent lymphoma clearance	[228]
	2020	Human	10 × Genomics	GEO: GSE139891	Identified multiple functionally linked subpopulations. Effectively provided a single cell-COO for ∼80% of DLBCLs and identified novel prognostic subgroups of DLBCL	[213]
	2022	Mouse	GEXSCOPE® platform	Correspondence with authors	Combination treatment with dacinostat (LAQ824) and a c-Fos inhibitor more potently inhibited tumor cells both in vitro and in vivo	[264]
	2022	Human	10 × Genomics	CNGBdb: CNP0001940	TME cells may promote DLBCL activation/survival through CD40- and BAFF-mediated signals. Coinhibitory signals through TIM3 and TIGIT may drive T-cell exhaustion in DLBCL. HBV infection likely contributes to malignant cell survival/immune evasion in DLBCL	[216]
	2022	Human	10 × Genomics	GEO: GSE182436	Expression of both PD-1 and A2aR potentially defined a subset of much more dysfunctional CD8+ T cells and was associated with inferior outcomes	[265]
Follicular lymphoma	2022	Human	10 × Genomics	EGA: EGAD00001008311	Largely updated the NHC taxonomy in human LNs, performed an analysis of disease status, and provided a rich resource and deeper insights into LN and lymphoma biology to advance lymphoma management and therapy	[112]
Mantle cell lymphoma	2020	Human	10 × Genomics	Correspondence with authors	The drug resistance mechanisms of different cell clusters included drug metabolism, DNA damage repair, apoptosis, and survival promotion	[226]
	2021	Human	10 × Genomics	EGA: EGAS00001005019	Due to the 17q gain, BIRC5/survivin expression was upregulated in resistant MCL tumor cells, and targeting BIRC5 resulted in marked tumor inhibition in preclinical models	[227]
B-cell lymphoma	2022	Human	10 × Genomics	EGA: EGAS00001005356	TIGIT blockade alone improved the antitumor function of CAR-T cells	[75]
Burkitt lymphoma	2022	Mouse	10 × Genomics	GEO: GSE190598	Paclitaxel promoted the clearance of lymphoma by directly evoking the phagocytic capability of macrophages. Activation of Src family tyrosine kinase signaling in macrophages by paclitaxel promoted phagocytosis against NHL cells	[225]
Peripheral T cell lymphoma	2022	Mouse	10 × Genomics	GEO: GSE166673	Vav1-Myo1f induces the development of GATA3+ Th2-like PTCL and accumulation of TAMs. TAMs can be targeted for the treatment of high-risk PTCL	[266]
	2022	Cell line	10 × Genomics	GEO: GSE204876	PTCL had distinct DNMT3A mutation patterns and prognostic outcomes. DNMT3A mutations were associated with an activated, cytotoxic phenotype in the PTCL-TBX21 subtype	[230]
Angioimmunoblastic T cell lymphoma	2022	Human and mouse	10 × Genomics	ENA: ERP138895 or EGA: EGAS00001006401	Tet2-deficient immune cells functioned as a niche for AITL development. ACH-derived GCB cells potentially undergo independent clonal evolution and support tumorigenesis in AITL via the CD40-CD40LG axis	[134]
Adult T cell leukemia-lymphoma	2021	Human	10 × Genomics	NBDC: JGAS000301	Identified possible molecular mechanisms of multistep tumorigenesis and revealed the transcriptomic changes in identical infected clones over time during multistep tumorigenesis	[267]
	2022	Human	10 × Genomics	GEO: GSE195674	Identified a novel subset of CAFs, suggesting a potential target for targeted therapy to enhance treatment	[268]
Cutaneous T cell lymphoma	2019	Human	10 × Genomics	Correspondence with authors	FOXP3 was identified as the most important factor to predict early disease in patients with CTCL. Transcriptome differences within a clonal tumor can be used to predict disease stage and thereby offer guidance for therapy	[73]
	2021	Human	10 × Genomics	GSE173205	Identified a specific panel of biomarkers that might be used for monitoring MF disease progression	[217]
	2022	Human	10 × Genomics	GSE124899 and GSE14658	New cellular clusters after progression of the therapy notably exhibited increased expression of the transcriptional factor FOXP3, raising the potential implication of an evolving mechanism of immune evasion	[209]
	2022	Human	10 × Genomics	GSE182861	Provided unprecedented new insights into MF/SS pathogenesis by reporting the transcriptional profile of malignant T-cell clones in the skin and blood of individual patients	[269]
	2022	Human	10 × Genomics	GSE197619	Identified putative precancerous circulating clonal CD4+ T-cell populations in patients with CTCL. The therapeutic potential of targeting CD82 and JAK was reported	[130]
	2022	Human	10 × Genomics	NCBI BioProject database PRJNA754592	Provided the first comprehensive compendium of genomic alterations in tCTCL, and identified potential prognostic signatures and novel therapeutic targets for a case of incurable T-cell lymphoma	[131]
	2022	Human	10 × Genomics	dbGaP: phs002933.v1.p1	Supported further study of KIR3DL2 expression and CD8 immune populations as predictive biomarkers of pembrolizumab response in patients with Sézary syndrome	[224]
T-cell lymphoma	2022	Zebrafish	10 × Genomics	GSE166646	Described the oncogenicity of IRF4 in vivo, its potential effects on T-cell development, and clonal evolution using a zebrafish model. IRF4-driven tumors were sensitive to a BRD inhibitor	[270]
Classic Hodgkin lymphoma	2021	Human	10 × Genomics	EGA: EGAS00001005541	This study strongly suggested the pathogenic importance of the CXCL13/CXCR5 axis and that PD-1+CXCL13+ T cells are a treatment target in LR-CHL	[271]