TISIDB

Summary
Symbol	CD8A
Name	CD8a molecule
Aliases	CD8; CD8 antigen, alpha polypeptide (p32); T-cell surface glycoprotein CD8 alpha chain; Leu2 T-lymphocyte an ......
Chromosomal Location	2p12
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	Isoform 1: Cell membrane Single-pass type I membrane protein. Note=CD8A localizes to lipid rafts only when associated with its partner CD8B. ; SUBCELLULAR LOCATION: Isoform 2: Secreted
Domain	PF07686 Immunoglobulin V-set domain
Function	Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primarily as a coreceptor for MHC class I molecule:peptide complex. The antigens presented by class I peptides are derived from cytosolic proteins while class II derived from extracellular proteins. Interacts simultaneously with the T-cell receptor (TCR) and the MHC class I proteins presented by antigen presenting cells (APCs). In turn, recruits the Src kinase LCK to the vicinity of the TCR-CD3 complex. LCK then initiates different intracellular signaling pathways by phosphorylating various substrates ultimately leading to lymphokine production, motility, adhesion and activation of cytotoxic T-lymphocytes (CTLs). This mechanism enables CTLs to recognize and eliminate infected cells and tumor cells. In NK-cells, the presence of CD8A homodimers at the cell surface provides a survival mechanism allowing conjugation and lysis of multiple target cells. CD8A homodimer molecules also promote the survival and differentiation of activated lymphocytes into memory CD8 T-cells.

> Gene Ontology [ TOP ]
Biological Process	GO:0002250 adaptive immune response GO:0002443 leukocyte mediated immunity GO:0002449 lymphocyte mediated immunity GO:0002456 T cell mediated immunity GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains GO:0002521 leukocyte differentiation GO:0007159 leukocyte cell-cell adhesion GO:0009615 response to virus GO:0019722 calcium-mediated signaling GO:0019882 antigen processing and presentation GO:0019932 second-messenger-mediated signaling GO:0030098 lymphocyte differentiation GO:0030217 T cell differentiation GO:0042110 T cell activation GO:0045065 cytotoxic T cell differentiation GO:0050848 regulation of calcium-mediated signaling GO:0050850 positive regulation of calcium-mediated signaling GO:0051607 defense response to virus GO:0070486 leukocyte aggregation GO:0070489 T cell aggregation GO:0071593 lymphocyte aggregation GO:0098542 defense response to other organism
Molecular Function	GO:0015026 coreceptor activity GO:0042287 MHC protein binding GO:0042288 MHC class I protein binding
Cellular Component	GO:0009897 external side of plasma membrane GO:0042101 T cell receptor complex GO:0043235 receptor complex GO:0098552 side of membrane GO:0098802 plasma membrane receptor complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04514 Cell adhesion molecules (CAMs) hsa04612 Antigen processing and presentation hsa04640 Hematopoietic cell lineage hsa04660 T cell receptor signaling pathway
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	CD8A
Name	CD8a molecule
Aliases	CD8; CD8 antigen, alpha polypeptide (p32); T-cell surface glycoprotein CD8 alpha chain; Leu2 T-lymphocyte an ......
Chromosomal Location	2p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CD8A 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 CD8A and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
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.
16882704	Melanoma	Promote immunity	We found that genetic removal of CTLA-4 induced activation and acquisition of effector functions in pmel-1 CD8 T cells, resulting in the rapid development of severe autoimmune vitiligo. These effects were abrogated by the removal of the CD4 T-cell population. Therefore, we propose that the lack of CTLA-4 on self/tumor antigen–specific CD8 T cells results in autoimmunity and tumor immunity only in the presence of nonspecific, dysregulated CD4 CTLA-4 / T cells.
16849468	lymphoma	Promote immunity	E.G7-OVA growth in the skin was not inhibited in immunodeficient Rag(-/-) or CD8 T cell-deficient mice, suggesting that CD8(+) CTLs mediate tumor elimination. CD8(+) T cell numbers were significantly increased in eyes of mice primed with E.G7-OVA, but few were detected in primary ocular tumors.

Summary
Symbol	CD8A
Name	CD8a molecule
Aliases	CD8; CD8 antigen, alpha polypeptide (p32); T-cell surface glycoprotein CD8 alpha chain; Leu2 T-lymphocyte an ......
Chromosomal Location	2p12
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 CD8A 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	CD8A
Name	CD8a molecule
Aliases	CD8; CD8 antigen, alpha polypeptide (p32); T-cell surface glycoprotein CD8 alpha chain; Leu2 T-lymphocyte an ......
Chromosomal Location	2p12
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 CD8A 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	-0.11	0.871
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.061	0.971
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.152	0.913
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.593	0.358
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	1.008	0.37
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.073	0.957
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.967	0.182
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.984	0.146
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.09	0.951
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	2.352	0.142
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	1.627	0.506
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.464	0.0527

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CD8A 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	0	0	0	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	0	0	1
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	6.2	4.9	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	25	14.3	10.7	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	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	CD8A
Name	CD8a molecule
Aliases	CD8; CD8 antigen, alpha polypeptide (p32); T-cell surface glycoprotein CD8 alpha chain; Leu2 T-lymphocyte an ......
Chromosomal Location	2p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CD8A. 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	CD8A
Name	CD8a molecule
Aliases	CD8; CD8 antigen, alpha polypeptide (p32); T-cell surface glycoprotein CD8 alpha chain; Leu2 T-lymphocyte an ......
Chromosomal Location	2p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CD8A. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CD8A. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CD8A
Name	CD8a molecule
Aliases	CD8; CD8 antigen, alpha polypeptide (p32); T-cell surface glycoprotein CD8 alpha chain; Leu2 T-lymphocyte an ......
Chromosomal Location	2p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CD8A. 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	CD8A
Name	CD8a molecule
Aliases	CD8; CD8 antigen, alpha polypeptide (p32); T-cell surface glycoprotein CD8 alpha chain; Leu2 T-lymphocyte an ......
Chromosomal Location	2p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CD8A expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CD8A
Name	CD8a molecule
Aliases	CD8; CD8 antigen, alpha polypeptide (p32); T-cell surface glycoprotein CD8 alpha chain; Leu2 T-lymphocyte an ......
Chromosomal Location	2p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CD8A and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CD8A
Name	CD8a molecule
Aliases	CD8; CD8 antigen, alpha polypeptide (p32); T-cell surface glycoprotein CD8 alpha chain; Leu2 T-lymphocyte an ......
Chromosomal Location	2p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CD8A collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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