TISIDB

Summary
Symbol	CD1D
Name	CD1d molecule
Aliases	CD1D antigen, d polypeptide; CD1d antigen; R3; HMC class I antigen-like glycoprotein CD1D; R3G1; T-cell surf ......
Chromosomal Location	1q23.1
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 Single-pass type I membrane protein Basolateral cell membrane Single-pass type I membrane protein Endosome membrane Single-pass type I membrane protein Lysosome membrane Single-pass type I membrane protein Endoplasmic reticulum membrane Single-pass type I membrane protein Note=Subject to intracellular trafficking between the cell membrane, endosomes and lysosomes.
Domain	PF07654 Immunoglobulin C1-set domain PF16497 MHC-I family domain
Function	Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T-cells.

> Gene Ontology [ TOP ]
Biological Process	GO:0002475 antigen processing and presentation via MHC class Ib GO:0002521 leukocyte differentiation GO:0002694 regulation of leukocyte activation GO:0002696 positive regulation of leukocyte activation GO:0007159 leukocyte cell-cell adhesion GO:0009595 detection of biotic stimulus GO:0016045 detection of bacterium GO:0019882 antigen processing and presentation GO:0019883 antigen processing and presentation of endogenous antigen GO:0019884 antigen processing and presentation of exogenous antigen GO:0022407 regulation of cell-cell adhesion GO:0022409 positive regulation of cell-cell adhesion GO:0030098 lymphocyte differentiation GO:0030217 T cell differentiation GO:0031349 positive regulation of defense response GO:0032943 mononuclear cell proliferation GO:0032944 regulation of mononuclear cell proliferation GO:0032946 positive regulation of mononuclear cell proliferation GO:0034113 heterotypic cell-cell adhesion GO:0042098 T cell proliferation GO:0042102 positive regulation of T cell proliferation GO:0042110 T cell activation GO:0042129 regulation of T cell proliferation GO:0045058 T cell selection GO:0045088 regulation of innate immune response GO:0045089 positive regulation of innate immune response GO:0045785 positive regulation of cell adhesion GO:0046651 lymphocyte proliferation GO:0048003 antigen processing and presentation of lipid antigen via MHC class Ib GO:0048006 antigen processing and presentation, endogenous lipid antigen via MHC class Ib GO:0048007 antigen processing and presentation, exogenous lipid antigen via MHC class Ib GO:0050670 regulation of lymphocyte proliferation GO:0050671 positive regulation of lymphocyte proliferation GO:0050863 regulation of T cell activation GO:0050865 regulation of cell activation GO:0050867 positive regulation of cell activation GO:0050870 positive regulation of T cell activation GO:0051249 regulation of lymphocyte activation GO:0051251 positive regulation of lymphocyte activation GO:0070486 leukocyte aggregation GO:0070489 T cell aggregation GO:0070661 leukocyte proliferation GO:0070663 regulation of leukocyte proliferation GO:0070665 positive regulation of leukocyte proliferation GO:0071593 lymphocyte aggregation GO:0098543 detection of other organism GO:0098581 detection of external biotic stimulus GO:1903037 regulation of leukocyte cell-cell adhesion GO:1903039 positive regulation of leukocyte cell-cell adhesion
Molecular Function	GO:0003823 antigen binding GO:0030881 beta-2-microglobulin binding GO:0030882 lipid antigen binding GO:0030883 endogenous lipid antigen binding GO:0030884 exogenous lipid antigen binding GO:0033218 amide binding GO:0042277 peptide binding GO:0042393 histone binding GO:0050839 cell adhesion molecule binding GO:0071723 lipopeptide binding
Cellular Component	GO:0005765 lysosomal membrane GO:0010008 endosome membrane GO:0016323 basolateral plasma membrane GO:0044440 endosomal part GO:0098852 lytic vacuole membrane

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04530 Tight junction hsa04640 Hematopoietic cell lineage
Reactome	R-HSA-1280218: Adaptive Immune System R-HSA-168256: Immune System R-HSA-198933: Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell

Summary
Symbol	CD1D
Name	CD1d molecule
Aliases	CD1D antigen, d polypeptide; CD1d antigen; R3; HMC class I antigen-like glycoprotein CD1D; R3G1; T-cell surf ......
Chromosomal Location	1q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CD1D 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 CD1D and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
27513300	Chronic myeloid leukemia	Promote immunity	Indeed, flow cytometry and confocal microscopy revealed that cell surface expression of CD1d was downregulated in CML mDCs, relative to healthy donor (HD) controls. In vitro treatment of CML mDCs with the Rho-associated protein kinase (ROCK) inhibitor Y-27632 partially restored both cell surface CD1d expression and CD1d-mediated antigen presentation, whereas it had no effect on HD mDCs. Our data support the conclusion that BCR-ABL-dependent ROCK, but not TK, is involved in CD1d downregulation.
24563871	T Lymphoblastic Lymphoma	Promote immunity	Invariant natural killer T (iNKT) cells comprise a lineage of CD1d-restricted glycolipid-reactive T lymphocytes with important roles in host immunity to cancer. iNKT cells indirectly participate in antitumor responses by inducing dendritic cell maturation and producing cytokines that promote tumor clearance by CD8+ T and NK cells. They also suggest that the induction of iNKT cell cytotoxic responses in situ might serve as a more effective strategy to prevent and/or treat CD1d+ cancers, such as T lymphoma.
18417738	B Acute Lymphoblastic Leukemia	Promote immunity (T cell function)	In tumor-bearing mice, we found that type I NKT cells conferred protection in a CD1d-dependent manner, whereas type II NKT cells exhibited inhibitory activity.
18323539	Laryngeal Carcinoma	Promote immunity (T cell function)	Although epithelial MHC class I and II expression was unchanged by reflux, expression of the nonclassical MHC molecule CD1d increased (P < 0.05, luminal layers). In vitro, laryngeal epithelial cells constitutively expressed CD1d. CD1d and MHC I expression were inversely related in all subjects, in a pattern which appears to be unique to the upper airway. Colocalization of natural killer T (NKT) cells with CD1d increased in patients (P < 0.01).
23065503	B-Cell cell lymphoma	Promote immunity (T cell function)	Invariant natural killer T cells recognize glycolipid antigens such as α-galactosylceramide presented by CD1d. Invariant natural killer T-cell lines from patients lysed CD1d-expressing targets. Irradiated α-galactosylceramide-treated leukemic cells elicited allogeneic and autologous invariant natural killer T-cell proliferation, and α-galactosylceramide treatment led to increased proliferation of conventional T cells in response to tumor.
19265113	Kidney carcinoma; colon carcinoma	Promote immunity; immnuotherapy target	The ability of anti-CD1d mAbs to coincidently activate CD1d(+) APCs to release IL-12 and inhibit CD1d-restricted type II NKT cells makes CD1d an exciting new target for immunotherapy of cancer based on tumor immunoregulation.
28465341	Chronic Lymphocytic Leukemia	Inhibit immunity (T cell function)	CD1d-restricted invariant natural killer T (iNKT) cells are innate-like T lymphocytes strongly implicated in tumor surveillance. We found that Tcl1-CLL cells express CD1d and that iNKT cells critically delay disease onset but become functionally impaired upon disease progression. In patients, disease progression correlates with high CD1d expression on CLL cells and impaired iNKT cells. Conversely, disease stability correlates with negative or low CD1d expression on CLL cells and normal iNKT cells, suggesting indirect leukemia control.
16585215	Osteosarcoma	Inhibit immunity	CD1d-restricted natural killer T cells can down-regulate tumor immunosurveillance independent of interleukin-4 receptor-signal transducer and activator of transcription 6 or transforming growth factor-beta.
25049283	neuroblastoma	Promote immunity (T cell function); essential for immunotherapy	We proposed that CAR expression in Vα24-invariant natural killer T (NKT) cells can build on the natural antitumor properties of these cells while their restriction by monomorphic CD1d limits toxicity. CAR.GD2 expression rendered NKT cells highly cytotoxic against NB cells without affecting their CD1d-dependent reactivity.
23860186	B16 Malignant Melanoma	Promote immunity (NK cell function)	Alpha-galactosylceramide (αGC), a lipid antigen present on CD1d molecules, is predicted to have clinical applications as a new class of adjuvant, because αGC strongly activates natural killer T (NKT) cells which produce large amounts of IFN-γ.
22817659	Osteosarcoma	Promote immunity	iNKT cells were cytotoxic against OS cells through a CD1d-dependent mechanism. iNKT cell treatment enhanced drug-induced OS cell death in a concentration-dependent manner and this effect was reduced in CD1d-silenced OS cells.
18760855	Colon Carcinoma	Promote immunity	Surgical subcutaneous tumor mass reduction resulted in the reduction of serum TGF-beta, the recovery of CD1d expressions on liver DCs and the improvement of antitumor effect of alpha-GalCer against metastatic liver tumor. These results suggested that tumor burden reduces CD1d expressions on liver DCs, thus impeding alpha-GalCer-mediated NK cell activation and antitumor activity in the liver.
25070854	lymphoma	Promote immunity	Furthermore, knockdown of Bcl-xL resulted in the loss of CD1d trafficking to lysosome-associated membrane protein 1(+) compartments.
21987790	Lung Carcinoma	Promote immunity	These findings suggest that CD1d-phenyl glycolipid complexes may interact with the same population of iNKT cells but with higher avidity and stability to drive Th1 polarization. Thus, this study provides a key to the rational design of Th1 biased CD1d reactive glycolipids in the future.
16818662	lymphoma	Promote immunity	We found that the addition of the iNKT ligand alpha-galactosylceramide (alphaGalCer) to peptide-loaded B cells overcame peptide-specific T-cell unresponsiveness and allowed for the generation of peptide-specific memory CTL immunity.

Summary
Symbol	CD1D
Name	CD1d molecule
Aliases	CD1D antigen, d polypeptide; CD1d antigen; R3; HMC class I antigen-like glycoprotein CD1D; R3G1; T-cell surf ......
Chromosomal Location	1q23.1
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 CD1D 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	CD1D
Name	CD1d molecule
Aliases	CD1D antigen, d polypeptide; CD1d antigen; R3; HMC class I antigen-like glycoprotein CD1D; R3G1; T-cell surf ......
Chromosomal Location	1q23.1
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 CD1D 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	0.077	0.817
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.256	0.655
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.057	0.909
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.257	0.571
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.277	0.786
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.234	0.85
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.521	0.236
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.069	0.168
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.105	0.903
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.303	0.719
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	0.255	0.832
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.224	0.221

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CD1D 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	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	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	0	2.7	-2.7	1
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	0	3.4	-3.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	5.9	-5.9	0.447
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	16.7	-16.7	0.429
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	7.9	0	7.9	0.26
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	13.6	0	13.6	0.279
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	0	0	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	0	0	1

Summary
Symbol	CD1D
Name	CD1d molecule
Aliases	CD1D antigen, d polypeptide; CD1d antigen; R3; HMC class I antigen-like glycoprotein CD1D; R3G1; T-cell surf ......
Chromosomal Location	1q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CD1D. 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	CD1D
Name	CD1d molecule
Aliases	CD1D antigen, d polypeptide; CD1d antigen; R3; HMC class I antigen-like glycoprotein CD1D; R3G1; T-cell surf ......
Chromosomal Location	1q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CD1D. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CD1D. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CD1D
Name	CD1d molecule
Aliases	CD1D antigen, d polypeptide; CD1d antigen; R3; HMC class I antigen-like glycoprotein CD1D; R3G1; T-cell surf ......
Chromosomal Location	1q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CD1D. 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	CD1D
Name	CD1d molecule
Aliases	CD1D antigen, d polypeptide; CD1d antigen; R3; HMC class I antigen-like glycoprotein CD1D; R3G1; T-cell surf ......
Chromosomal Location	1q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CD1D expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CD1D
Name	CD1d molecule
Aliases	CD1D antigen, d polypeptide; CD1d antigen; R3; HMC class I antigen-like glycoprotein CD1D; R3G1; T-cell surf ......
Chromosomal Location	1q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CD1D and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CD1D
Name	CD1d molecule
Aliases	CD1D antigen, d polypeptide; CD1d antigen; R3; HMC class I antigen-like glycoprotein CD1D; R3G1; T-cell surf ......
Chromosomal Location	1q23.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CD1D collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting CD1D.

ID	Name	Drug Type	Targets	#Targets
DB04661	Cis-tetracosenoyl sulfatide	Small Molecule	CD1D	1

Browse CD1D