TISIDB

Summary
Symbol	MS4A1
Name	membrane-spanning 4-domains, subfamily A, member 1
Aliases	Bp35; CVID5; LEU-16; B-lymphocyte cell-surface antigen B1; CD20 antigen; CD20 receptor; leukocyte surface an ......
Chromosomal Location	11q12.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Cell membrane Multi-pass membrane protein Cell membrane Lipid-anchor
Domain	PF04103 CD20-like family
Function	This protein may be involved in the regulation of B-cell activation and proliferation.

> Gene Ontology [ TOP ]
Biological Process	GO:0006959 humoral immune response GO:0032943 mononuclear cell proliferation GO:0042100 B cell proliferation GO:0042113 B cell activation GO:0046651 lymphocyte proliferation GO:0070661 leukocyte proliferation
Molecular Function	GO:0003823 antigen binding GO:0005154 epidermal growth factor receptor binding GO:0023023 MHC protein complex binding GO:0023026 MHC class II protein complex binding GO:0070851 growth factor receptor binding
Cellular Component	GO:0009897 external side of plasma membrane GO:0098552 side of membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04640 Hematopoietic cell lineage
Reactome	-

Summary
Symbol	MS4A1
Name	membrane-spanning 4-domains, subfamily A, member 1
Aliases	Bp35; CVID5; LEU-16; B-lymphocyte cell-surface antigen B1; CD20 antigen; CD20 receptor; leukocyte surface an ......
Chromosomal Location	11q12.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between MS4A1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

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Literatures describing the relation between MS4A1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
16520392	Lymphoma	Promote immunity	CD20 monoclonal antibody (mAb) immunotherapy is effective for lymphoma and autoimmune disease.
27511870	B-Cell Non-Hodgkin Lymphoma	Promote immunity	Here, we describe the use of the anti-CD20 monoclonal antibody (mAb), rituximab-IR700 APC for NIR-PIT of B-cell lymphoma in two CD20-expressing lymphoma mouse models. Rituximab-IR700 showed high tumor accumulation and high target-to-background ratio in?vivo. Tumor growth was significantly inhibited by NIR-PIT in comparison with the other groups. In conclusion, anti-CD20 rituximab-IR700 works as a highly effective APC for NIR-PIT against B-cell lymphoma.
22354003	B-cell Lymphoma; Chronic Lymphocytic Leukemia	Promote immunity	Here, we reveal that the induction of PCD by these mAbs, including the type II anti-CD20 mAb GA101 (obinutuzumab), directly correlates with their ability to produce reactive oxygen species (ROS) in human B-lymphoma cell lines and primary B-cell chronic lymphocytic leukemia cells. Instead, ROS generation was mediated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.
22308288	Mantle Cell Lymphoma	Promote immunity	We conducted a pilot clinical trial testing a "third-generation" CD20-specific CAR with CD28 and 4-1BB costimulatory domains in patients with relapsed indolent B-cell and mantle cell lymphomas. In conclusion, adoptive immunotherapy with CD20-specific T cells was well tolerated and was associated with antitumor activity.
18593929	Non-Hodgkin Lymphoma	Promote immunity	Improved therapeutic results by pretargeted radioimmunotherapy of non-Hodgkin's lymphoma with a new recombinant, trivalent, anti-CD20, bispecific antibody.
17530016	B-Cell Non-Hodgkin Lymphoma	Promote immunity	Rituximab (chimeric anti-CD20 monoclonal antibody) is the first Food and Drug Administration approved antitumor antibody and is used in the treatment of B-non-Hodgkin's lymphoma (B-NHL). Rituximab has been shown to inhibit the p38 mitogen-activated protein kinase, nuclear factor-kappaB (NF-kappaB), extracellular signal-regulated kinase 1/2 (ERK 1/2) and AKT antiapoptotic survival pathways, all of which result in upregulation of phosphatase and tensin homolog deleted on chromosome ten and Raf kinase inhibitor protein and in the downregulation of antiapoptotic gene products (particularly Bcl-2, Bcl-(xL) and Mcl-1), and resulting in chemo/immunosensitization. Further, rituximab treatment inhibits the overexpressed transcription repressor Yin Yang 1 (YY1), which negatively regulates Fas and DR5 expression and its inhibition leads to sensitization to Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis.
17530015	B-Cell Non-Hodgkin Lymphoma	Promote immunity	Radioimmunotherapy for B-cell lymphoma: Y90 ibritumomab tiuxetan and I(131) tositumomab. Radioimmunotherapy, targeting the CD20 antigen, in B-cell lymphoma has clearly demonstrated efficacy and tolerability over the preceding 15 years. Both demonstrate high-response rates and durability of remission in the relapsed/refractory disease setting.
16899613	Bladder carcinoma	Promote immunity	Immunohistochemical staining for HLA class I, CD4, CD8, CD20, CD68, TIA-1, S-100, and FOXP3 was carried out on specimens from 30 patients who underwent BCG immunotherapy from whom both pretreatment and posttreatment specimens were obtained. Our data show that expression of HLA class I molecules on tumor cells contributes significantly to the therapeutic effect of BCG immunotherapy for bladder cancer. It is suggested that CTLs may be one of main effectors in this therapy.

Summary
Symbol	MS4A1
Name	membrane-spanning 4-domains, subfamily A, member 1
Aliases	Bp35; CVID5; LEU-16; B-lymphocyte cell-surface antigen B1; CD20 antigen; CD20 receptor; leukocyte surface an ......
Chromosomal Location	11q12.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of MS4A1 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	MS4A1
Name	membrane-spanning 4-domains, subfamily A, member 1
Aliases	Bp35; CVID5; LEU-16; B-lymphocyte cell-surface antigen B1; CD20 antigen; CD20 receptor; leukocyte surface an ......
Chromosomal Location	11q12.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of MS4A1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.46	0.544
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	1.772	0.134
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.511	0.625
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.024	0.977
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.053	0.97
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.129	0.934
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	1.477	0.0942
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.378	0.309
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	1.9	0.149
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	1.474	0.185
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.844	0.592
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.045	0.907

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of MS4A1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	1.4	2.3	0.469
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	1.7	2	0.532
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	0	11.1	0.36
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	20	0	20	0.357
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	5.3	0	5.3	0.507
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	9.1	0	9.1	0.519
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	7.7	-7.7	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	8.3	-8.3	1

Summary
Symbol	MS4A1
Name	membrane-spanning 4-domains, subfamily A, member 1
Aliases	Bp35; CVID5; LEU-16; B-lymphocyte cell-surface antigen B1; CD20 antigen; CD20 receptor; leukocyte surface an ......
Chromosomal Location	11q12.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of MS4A1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	MS4A1
Name	membrane-spanning 4-domains, subfamily A, member 1
Aliases	Bp35; CVID5; LEU-16; B-lymphocyte cell-surface antigen B1; CD20 antigen; CD20 receptor; leukocyte surface an ......
Chromosomal Location	11q12.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of MS4A1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by MS4A1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	MS4A1
Name	membrane-spanning 4-domains, subfamily A, member 1
Aliases	Bp35; CVID5; LEU-16; B-lymphocyte cell-surface antigen B1; CD20 antigen; CD20 receptor; leukocyte surface an ......
Chromosomal Location	11q12.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of MS4A1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	MS4A1
Name	membrane-spanning 4-domains, subfamily A, member 1
Aliases	Bp35; CVID5; LEU-16; B-lymphocyte cell-surface antigen B1; CD20 antigen; CD20 receptor; leukocyte surface an ......
Chromosomal Location	11q12.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of MS4A1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	MS4A1
Name	membrane-spanning 4-domains, subfamily A, member 1
Aliases	Bp35; CVID5; LEU-16; B-lymphocyte cell-surface antigen B1; CD20 antigen; CD20 receptor; leukocyte surface an ......
Chromosomal Location	11q12.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between MS4A1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	MS4A1
Name	membrane-spanning 4-domains, subfamily A, member 1
Aliases	Bp35; CVID5; LEU-16; B-lymphocyte cell-surface antigen B1; CD20 antigen; CD20 receptor; leukocyte surface an ......
Chromosomal Location	11q12.2
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting MS4A1 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting MS4A1.

ID	Name	Drug Type	Targets	#Targets
DB00073	Rituximab	Biotech	C1QA, C1QB, C1QC, C1R, C1S, FCGR1A, FCGR2A, FCGR2B, FCGR2C, FCGR3A ......	12
DB00078	Ibritumomab tiuxetan	Biotech	C1QA, C1QB, C1QC, C1R, C1S, FCGR1A, FCGR2A, FCGR2B, FCGR2C, FCGR3A ......	12
DB00081	Tositumomab	Biotech	C1QA, C1QB, C1QC, C1R, FCGR1A, FCGR2A, FCGR2B, FCGR2C, FCGR3A, FCG ......	11
DB06650	Ofatumumab	Biotech	MS4A1	1
DB08935	Obinutuzumab	Biotech	MS4A1	1
DB09336	Technetium Tc-99m nofetumomab merpentan	Small Molecule	EPCAM, MS4A1	2
DB11988	Ocrelizumab	Biotech	MS4A1	1

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