TISIDB

Summary
Symbol	ALCAM
Name	activated leukocyte cell adhesion molecule
Aliases	CD166; MEMD; activated leucocyte cell adhesion molecule; CD antigen CD166; CD166 antigen
Chromosomal Location	3q13.1
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 Cell projection, axon Cell projection, dendrite Note=Detected at the immunological synapse, i.e, at the contact zone between antigen-presenting dendritic cells and T-cells (PubMed:15294938, PubMed:16352806). Colocalizes with CD6 and the TCR/CD3 complex at the immunological synapse (PubMed:15294938). ; SUBCELLULAR LOCATION: Isoform 3: Secreted
Domain	PF08205 CD80-like C2-set immunoglobulin domain
Function	Cell adhesion molecule that mediates both heterotypic cell-cell contacts via its interaction with CD6, as well as homotypic cell-cell contacts (PubMed:7760007, PubMed:15496415, PubMed:15048703, PubMed:16352806, PubMed:23169771, PubMed:24945728). Promotes T-cell activation and proliferation via its interactions with CD6 (PubMed:15048703, PubMed:16352806, PubMed:24945728). Contributes to the formation and maturation of the immunological synapse via its interactions with CD6 (PubMed:15294938, PubMed:16352806). Mediates homotypic interactions with cells that express ALCAM (PubMed:15496415, PubMed:16352806). Required for normal hematopoietic stem cell engraftment in the bone marrow (PubMed:24740813). Mediates attachment of dendritic cells onto endothelial cells via homotypic interaction (PubMed:23169771). Inhibits endothelial cell migration and promotes endothelial tube formation via homotypic interactions (PubMed:15496415, PubMed:23169771). Required for normal organization of the lymph vessel network. Required for normal hematopoietic stem cell engraftment in the bone marrow. Plays a role in hematopoiesis; required for normal numbers of hematopoietic stem cells in bone marrow. Promotes in vitro osteoblast proliferation and differentiation (By similarity). Promotes neurite extension, axon growth and axon guidance; axons grow preferentially on surfaces that contain ALCAM. Mediates outgrowth and pathfinding for retinal ganglion cell axons (By similarity). ; FUNCTION: Isoform 3: Inhibits activities of membrane-bound isoforms by competing for the same interaction partners. Inhibits cell attachment via homotypic interactions. Promotes endothelial cell migration. Inhibits endothelial cell tube formation.

> Gene Ontology [ TOP ]
Biological Process	GO:0002250 adaptive immune response GO:0007157 heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules GO:0007409 axonogenesis GO:0007411 axon guidance GO:0008045 motor neuron axon guidance GO:0016049 cell growth GO:0031290 retinal ganglion cell axon guidance GO:0048588 developmental cell growth GO:0048667 cell morphogenesis involved in neuron differentiation GO:0048675 axon extension GO:0048846 axon extension involved in axon guidance GO:0060560 developmental growth involved in morphogenesis GO:0061564 axon development GO:0097485 neuron projection guidance GO:0098742 cell-cell adhesion via plasma-membrane adhesion molecules GO:1902284 neuron projection extension involved in neuron projection guidance GO:1990138 neuron projection extension
Molecular Function	-
Cellular Component	GO:0001772 immunological synapse GO:0005924 cell-substrate adherens junction GO:0005925 focal adhesion GO:0009897 external side of plasma membrane GO:0030055 cell-substrate junction GO:0030424 axon GO:0030425 dendrite GO:0042101 T cell receptor complex GO:0043025 neuronal cell body GO:0043235 receptor complex GO:0044297 cell body GO:0098552 side of membrane GO:0098802 plasma membrane receptor complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04514 Cell adhesion molecules (CAMs)
Reactome	R-HSA-422475: Axon guidance R-HSA-1266738: Developmental Biology R-HSA-373760: L1CAM interactions

Summary
Symbol	ALCAM
Name	activated leukocyte cell adhesion molecule
Aliases	CD166; MEMD; activated leucocyte cell adhesion molecule; CD antigen CD166; CD166 antigen
Chromosomal Location	3q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between ALCAM 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 ALCAM and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
27208904	Melanoma	Inhibit immunity (T cell function)	The cryo-induced ALCAM(+) cells including CD45(-) mesenchymal stem/stromal cells, CD11b(+)Gr1(+) myeloid-derived suppressor cells, and CD4(+)Foxp3(+) regulatory T cells significantly suppressed interferon γ production and cytotoxicity of tumour-specific CD8(+) T cells via ALCAM expressed in these cells.
29263213	T Acute Lymphoblastic Leukemia	Inhibit immunity (T cell function)	Knockdown of CD166 in primary human T cells by nucleofection abolished the capacity of ILT3.Fc to inhibit CD4+ Th cell proliferation and to induce the generation of CD8+CD28- T suppressor cells.
27813511	Colorectal Cancinoma	Inhibit immunity	Moreover, colorectal carcinomas characterized by lack of CDX2 and prominent expression of ALCAM frequently (71%) showed CD274 positivity. This might suggest association of CD274 expression with 'stem-like' phenotype.

Summary
Symbol	ALCAM
Name	activated leukocyte cell adhesion molecule
Aliases	CD166; MEMD; activated leucocyte cell adhesion molecule; CD antigen CD166; CD166 antigen
Chromosomal Location	3q13.1
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 ALCAM 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	ALCAM
Name	activated leukocyte cell adhesion molecule
Aliases	CD166; MEMD; activated leucocyte cell adhesion molecule; CD antigen CD166; CD166 antigen
Chromosomal Location	3q13.1
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 ALCAM 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	-0.344	0.477
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.386	0.781
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.306	0.754
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.4	0.367
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.028	0.988
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.941	0.696
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.122	0.826
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.115	0.945
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.331	0.852
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.115	0.941
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	1.086	0.615
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.053	0.761

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of ALCAM 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	11.1	2.7	8.4	0.12
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	11.1	3.4	7.7	0.176
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	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	9.1	-9.1	0.458
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	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	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	5.3	3.7	1.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	7.7	-3.2	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	ALCAM
Name	activated leukocyte cell adhesion molecule
Aliases	CD166; MEMD; activated leucocyte cell adhesion molecule; CD antigen CD166; CD166 antigen
Chromosomal Location	3q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ALCAM. 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	ALCAM
Name	activated leukocyte cell adhesion molecule
Aliases	CD166; MEMD; activated leucocyte cell adhesion molecule; CD antigen CD166; CD166 antigen
Chromosomal Location	3q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ALCAM. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ALCAM. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	ALCAM
Name	activated leukocyte cell adhesion molecule
Aliases	CD166; MEMD; activated leucocyte cell adhesion molecule; CD antigen CD166; CD166 antigen
Chromosomal Location	3q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ALCAM. 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	ALCAM
Name	activated leukocyte cell adhesion molecule
Aliases	CD166; MEMD; activated leucocyte cell adhesion molecule; CD antigen CD166; CD166 antigen
Chromosomal Location	3q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of ALCAM expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	ALCAM
Name	activated leukocyte cell adhesion molecule
Aliases	CD166; MEMD; activated leucocyte cell adhesion molecule; CD antigen CD166; CD166 antigen
Chromosomal Location	3q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between ALCAM and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	ALCAM
Name	activated leukocyte cell adhesion molecule
Aliases	CD166; MEMD; activated leucocyte cell adhesion molecule; CD antigen CD166; CD166 antigen
Chromosomal Location	3q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting ALCAM collected from DrugBank database.

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

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