TISIDB

Summary
Symbol	CASP8
Name	caspase 8, apoptosis-related cysteine peptidase
Aliases	MCH5; MACH; FLICE; Casp-8; caspase 8, apoptosis-related cysteine protease; ALPS2B; CAP4; FADD-homologous ICE ......
Chromosomal Location	2q33-q34
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	Cytoplasm.
Domain	PF01335 Death effector domain
Function	Most upstream protease of the activation cascade of caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1A induced cell death. Binding to the adapter molecule FADD recruits it to either receptor. The resulting aggregate called death-inducing signaling complex (DISC) performs CASP8 proteolytic activation. The active dimeric enzyme is then liberated from the DISC and free to activate downstream apoptotic proteases. Proteolytic fragments of the N-terminal propeptide (termed CAP3, CAP5 and CAP6) are likely retained in the DISC. Cleaves and activates CASP3, CASP4, CASP6, CASP7, CASP9 and CASP10. May participate in the GZMB apoptotic pathways. Cleaves ADPRT. Hydrolyzes the small-molecule substrate, Ac-Asp-Glu-Val-Asp-\|-AMC. Likely target for the cowpox virus CRMA death inhibitory protein. Isoform 5, isoform 6, isoform 7 and isoform 8 lack the catalytic site and may interfere with the pro-apoptotic activity of the complex.

> Gene Ontology [ TOP ]
Biological Process	GO:0001701 in utero embryonic development GO:0001844 protein insertion into mitochondrial membrane involved in apoptotic signaling pathway GO:0001890 placenta development GO:0001892 embryonic placenta development GO:0001959 regulation of cytokine-mediated signaling pathway GO:0002218 activation of innate immune response GO:0002221 pattern recognition receptor signaling pathway GO:0002224 toll-like receptor signaling pathway GO:0002237 response to molecule of bacterial origin GO:0002521 leukocyte differentiation GO:0002573 myeloid leukocyte differentiation GO:0002753 cytoplasmic pattern recognition receptor signaling pathway GO:0002756 MyD88-independent toll-like receptor signaling pathway GO:0002757 immune response-activating signal transduction GO:0002758 innate immune response-activating signal transduction GO:0002761 regulation of myeloid leukocyte differentiation GO:0002763 positive regulation of myeloid leukocyte differentiation GO:0002764 immune response-regulating signaling pathway GO:0006839 mitochondrial transport GO:0006919 activation of cysteine-type endopeptidase activity involved in apoptotic process GO:0006921 cellular component disassembly involved in execution phase of apoptosis GO:0007006 mitochondrial membrane organization GO:0007159 leukocyte cell-cell adhesion GO:0007249 I-kappaB kinase/NF-kappaB signaling GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors GO:0008637 apoptotic mitochondrial changes GO:0009266 response to temperature stimulus GO:0009409 response to cold GO:0009612 response to mechanical stimulus GO:0010035 response to inorganic substance GO:0010038 response to metal ion GO:0010466 negative regulation of peptidase activity GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway GO:0010821 regulation of mitochondrion organization GO:0010822 positive regulation of mitochondrion organization GO:0010939 regulation of necrotic cell death GO:0010950 positive regulation of endopeptidase activity GO:0010951 negative regulation of endopeptidase activity GO:0010952 positive regulation of peptidase activity GO:0016485 protein processing GO:0019048 modulation by virus of host morphology or physiology GO:0019050 suppression by virus of host apoptotic process GO:0019054 modulation by virus of host process GO:0030099 myeloid cell differentiation GO:0030101 natural killer cell activation GO:0030225 macrophage differentiation GO:0030522 intracellular receptor signaling pathway GO:0031349 positive regulation of defense response GO:0031638 zymogen activation GO:0032025 response to cobalt ion GO:0032355 response to estradiol GO:0032496 response to lipopolysaccharide GO:0033209 tumor necrosis factor-mediated signaling pathway GO:0033668 negative regulation by symbiont of host apoptotic process GO:0034612 response to tumor necrosis factor GO:0035666 TRIF-dependent toll-like receptor signaling pathway GO:0035794 positive regulation of mitochondrial membrane permeability GO:0035821 modification of morphology or physiology of other organism GO:0035872 nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway GO:0036462 TRAIL-activated apoptotic signaling pathway GO:0039506 modulation by virus of host molecular function GO:0039507 suppression by virus of host molecular function GO:0039513 suppression by virus of host catalytic activity GO:0039516 modulation by virus of host catalytic activity GO:0039526 modulation by virus of host apoptotic process GO:0039650 suppression by virus of host cysteine-type endopeptidase activity involved in apoptotic process GO:0042110 T cell activation GO:0042113 B cell activation GO:0043122 regulation of I-kappaB kinase/NF-kappaB signaling GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling GO:0043124 negative regulation of I-kappaB kinase/NF-kappaB signaling GO:0043154 negative regulation of cysteine-type endopeptidase activity involved in apoptotic process GO:0043280 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process GO:0043281 regulation of cysteine-type endopeptidase activity involved in apoptotic process GO:0044003 modification by symbiont of host morphology or physiology GO:0044068 modulation by symbiont of host cellular process GO:0044359 modulation of molecular function in other organism GO:0044362 negative regulation of molecular function in other organism GO:0044531 modulation of programmed cell death in other organism GO:0044532 modulation of apoptotic process in other organism GO:0045088 regulation of innate immune response GO:0045089 positive regulation of innate immune response GO:0045471 response to ethanol GO:0045637 regulation of myeloid cell differentiation GO:0045639 positive regulation of myeloid cell differentiation GO:0045649 regulation of macrophage differentiation GO:0045651 positive regulation of macrophage differentiation GO:0045861 negative regulation of proteolysis GO:0045862 positive regulation of proteolysis GO:0046677 response to antibiotic GO:0046902 regulation of mitochondrial membrane permeability GO:0048568 embryonic organ development GO:0048608 reproductive structure development GO:0051204 protein insertion into mitochondrial membrane GO:0051205 protein insertion into membrane GO:0051259 protein oligomerization GO:0051291 protein heterooligomerization GO:0051346 negative regulation of hydrolase activity GO:0051604 protein maturation GO:0051701 interaction with host GO:0051702 interaction with symbiont GO:0051817 modification of morphology or physiology of other organism involved in symbiotic interaction GO:0051851 modification by host of symbiont morphology or physiology GO:0052040 modulation by symbiont of host programmed cell death GO:0052041 negative regulation by symbiont of host programmed cell death GO:0052053 negative regulation by symbiont of host catalytic activity GO:0052055 modulation by symbiont of host molecular function GO:0052056 negative regulation by symbiont of host molecular function GO:0052148 modulation by symbiont of host catalytic activity GO:0052150 modulation by symbiont of host apoptotic process GO:0052199 negative regulation of catalytic activity in other organism involved in symbiotic interaction GO:0052203 modulation of catalytic activity in other organism involved in symbiotic interaction GO:0052204 negative regulation of molecular function in other organism involved in symbiotic interaction GO:0052205 modulation of molecular function in other organism involved in symbiotic interaction GO:0052248 modulation of programmed cell death in other organism involved in symbiotic interaction GO:0052422 modulation by host of symbiont catalytic activity GO:0052428 modification by host of symbiont molecular function GO:0052433 modulation by organism of apoptotic process in other organism involved in symbiotic interaction GO:0052490 negative regulation by organism of programmed cell death in other organism involved in symbiotic interaction GO:0052547 regulation of peptidase activity GO:0052548 regulation of endopeptidase activity GO:0060706 cell differentiation involved in embryonic placenta development GO:0060711 labyrinthine layer development GO:0060715 syncytiotrophoblast cell differentiation involved in labyrinthine layer development GO:0060759 regulation of response to cytokine stimulus GO:0061458 reproductive system development GO:0070265 necrotic cell death GO:0070423 nucleotide-binding oligomerization domain containing signaling pathway GO:0070486 leukocyte aggregation GO:0070489 T cell aggregation GO:0070585 protein localization to mitochondrion GO:0071214 cellular response to abiotic stimulus GO:0071260 cellular response to mechanical stimulus GO:0071356 cellular response to tumor necrosis factor GO:0071407 cellular response to organic cyclic compound GO:0071496 cellular response to external stimulus GO:0071550 death-inducing signaling complex assembly GO:0071593 lymphocyte aggregation GO:0072655 establishment of protein localization to mitochondrion GO:0072657 protein localization to membrane GO:0090150 establishment of protein localization to membrane GO:0090559 regulation of membrane permeability GO:0097191 extrinsic apoptotic signaling pathway GO:0097194 execution phase of apoptosis GO:0097202 activation of cysteine-type endopeptidase activity GO:0097296 activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway GO:0097305 response to alcohol GO:0097345 mitochondrial outer membrane permeabilization GO:1900739 regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway GO:1900740 positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway GO:1901028 regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway GO:1901030 positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway GO:1902041 regulation of extrinsic apoptotic signaling pathway via death domain receptors GO:1902042 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors GO:1902105 regulation of leukocyte differentiation GO:1902107 positive regulation of leukocyte differentiation GO:1902108 regulation of mitochondrial membrane permeability involved in apoptotic process GO:1902110 positive regulation of mitochondrial membrane permeability involved in apoptotic process GO:1902532 negative regulation of intracellular signal transduction GO:1902686 mitochondrial outer membrane permeabilization involved in programmed cell death GO:1903706 regulation of hemopoiesis GO:1903708 positive regulation of hemopoiesis GO:1903747 regulation of establishment of protein localization to mitochondrion GO:1903749 positive regulation of establishment of protein localization to mitochondrion GO:1903829 positive regulation of cellular protein localization GO:1904951 positive regulation of establishment of protein localization GO:2000116 regulation of cysteine-type endopeptidase activity GO:2000117 negative regulation of cysteine-type endopeptidase activity GO:2001056 positive regulation of cysteine-type endopeptidase activity GO:2001233 regulation of apoptotic signaling pathway GO:2001234 negative regulation of apoptotic signaling pathway GO:2001235 positive regulation of apoptotic signaling pathway GO:2001236 regulation of extrinsic apoptotic signaling pathway GO:2001237 negative regulation of extrinsic apoptotic signaling pathway GO:2001267 regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway GO:2001269 positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway
Molecular Function	GO:0004175 endopeptidase activity GO:0004197 cysteine-type endopeptidase activity GO:0005123 death receptor binding GO:0005126 cytokine receptor binding GO:0005164 tumor necrosis factor receptor binding GO:0008234 cysteine-type peptidase activity GO:0031625 ubiquitin protein ligase binding GO:0032813 tumor necrosis factor receptor superfamily binding GO:0035877 death effector domain binding GO:0044389 ubiquitin-like protein ligase binding GO:0097110 scaffold protein binding GO:0097153 cysteine-type endopeptidase activity involved in apoptotic process GO:0097199 cysteine-type endopeptidase activity involved in apoptotic signaling pathway
Cellular Component	GO:0005741 mitochondrial outer membrane GO:0019867 outer membrane GO:0031264 death-inducing signaling complex GO:0031265 CD95 death-inducing signaling complex GO:0031968 organelle outer membrane GO:0044297 cell body GO:0044445 cytosolic part GO:0045121 membrane raft GO:0097342 ripoptosome GO:0098589 membrane region GO:0098857 membrane microdomain

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04115 p53 signaling pathway hsa04210 Apoptosis hsa04620 Toll-like receptor signaling pathway hsa04621 NOD-like receptor signaling pathway hsa04622 RIG-I-like receptor signaling pathway hsa04668 TNF signaling pathway
Reactome	R-HSA-166054: Activated TLR4 signalling R-HSA-75108: Activation, myristolyation of BID and translocation to mitochondria R-HSA-109581: Apoptosis R-HSA-111465: Apoptotic cleavage of cellular proteins R-HSA-75153: Apoptotic execution phase R-HSA-5621481: C-type lectin receptors (CLRs) R-HSA-5218900: CASP8 activity is inhibited R-HSA-5607764: CLEC7A (Dectin-1) signaling R-HSA-5660668: CLEC7A/inflammasome pathway R-HSA-5357769: Caspase activation via extrinsic apoptotic signalling pathway R-HSA-264870: Caspase-mediated cleavage of cytoskeletal proteins R-HSA-73887: Death Receptor Signalling R-HSA-69416: Dimerization of procaspase-8 R-HSA-75157: FasL/ CD95L signaling R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-109606: Intrinsic Pathway for Apoptosis R-HSA-140534: Ligand-dependent caspase activation R-HSA-166166: MyD88-independent TLR3/TLR4 cascade R-HSA-933543: NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 R-HSA-168638: NOD1/2 Signaling Pathway R-HSA-168643: Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways R-HSA-5357801: Programmed Cell Death R-HSA-168928: RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways R-HSA-5213460: RIPK1-mediated regulated necrosis R-HSA-5218859: Regulated Necrosis R-HSA-3371378: Regulation by c-FLIP R-HSA-5357905: Regulation of TNFR1 signaling R-HSA-5675482: Regulation of necroptotic cell death R-HSA-162582: Signal Transduction R-HSA-75893: TNF signaling R-HSA-5357786: TNFR1-induced proapoptotic signaling R-HSA-75158: TRAIL signaling R-HSA-937061: TRIF-mediated TLR3/TLR4 signaling R-HSA-2562578: TRIF-mediated programmed cell death R-HSA-168164: Toll Like Receptor 3 (TLR3) Cascade R-HSA-166016: Toll Like Receptor 4 (TLR4) Cascade R-HSA-168898: Toll-Like Receptors Cascades

> KEGG and Reactome Pathway

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KEGG

hsa04115 p53 signaling pathway
hsa04210 Apoptosis
hsa04620 Toll-like receptor signaling pathway
hsa04621 NOD-like receptor signaling pathway
hsa04622 RIG-I-like receptor signaling pathway
hsa04668 TNF signaling pathway

Reactome

R-HSA-166054: Activated TLR4 signalling
R-HSA-75108: Activation, myristolyation of BID and translocation to mitochondria
R-HSA-109581: Apoptosis
R-HSA-111465: Apoptotic cleavage of cellular proteins
R-HSA-75153: Apoptotic execution phase
R-HSA-5621481: C-type lectin receptors (CLRs)
R-HSA-5218900: CASP8 activity is inhibited
R-HSA-5607764: CLEC7A (Dectin-1) signaling
R-HSA-5660668: CLEC7A/inflammasome pathway
R-HSA-5357769: Caspase activation via extrinsic apoptotic signalling pathway
R-HSA-264870: Caspase-mediated cleavage of cytoskeletal proteins
R-HSA-73887: Death Receptor Signalling
R-HSA-69416: Dimerization of procaspase-8
R-HSA-75157: FasL/ CD95L signaling
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-109606: Intrinsic Pathway for Apoptosis
R-HSA-140534: Ligand-dependent caspase activation
R-HSA-166166: MyD88-independent TLR3/TLR4 cascade
R-HSA-933543: NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10
R-HSA-168638: NOD1/2 Signaling Pathway
R-HSA-168643: Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
R-HSA-5357801: Programmed Cell Death
R-HSA-168928: RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways
R-HSA-5213460: RIPK1-mediated regulated necrosis
R-HSA-5218859: Regulated Necrosis
R-HSA-3371378: Regulation by c-FLIP
R-HSA-5357905: Regulation of TNFR1 signaling
R-HSA-5675482: Regulation of necroptotic cell death
R-HSA-162582: Signal Transduction
R-HSA-75893: TNF signaling
R-HSA-5357786: TNFR1-induced proapoptotic signaling
R-HSA-75158: TRAIL signaling
R-HSA-937061: TRIF-mediated TLR3/TLR4 signaling
R-HSA-2562578: TRIF-mediated programmed cell death
R-HSA-168164: Toll Like Receptor 3 (TLR3) Cascade
R-HSA-166016: Toll Like Receptor 4 (TLR4) Cascade
R-HSA-168898: Toll-Like Receptors Cascades

Summary
Symbol	CASP8
Name	caspase 8, apoptosis-related cysteine peptidase
Aliases	MCH5; MACH; FLICE; Casp-8; caspase 8, apoptosis-related cysteine protease; ALPS2B; CAP4; FADD-homologous ICE ......
Chromosomal Location	2q33-q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between CASP8 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 CASP8 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
25600646	Hepatocellular Carcinoma	Inhibit immunity (T cell function)	TLR2 limits development of hepatocellular carcinoma by reducing IL18-mediated immunosuppression. IL18 production was mediated by caspase-8 insofar as the decrease in its silencing was sufficient to attenuate levels of mature IL18 in Tlr2(-/-) mice.
21282461	Bladder Carcinoma	Promote immunity	We demonstrate that receptor-interacting protein 1 (RIP1) is an integral component of this complex and is required for CD40 ligand-induced caspase-8 activation and tumor cell killing.
17450141	Lung Carcinoma; Esophageal Carcinoma; Gastric Carcinoma; Colorectal Carcinoma; Cervical Carcinoma; Breast Carcinoma	Inhibit immunity (T cell function)	Using a haplotype-tagging SNP approach, we identified a six-nucleotide deletion (-652 6N del) variant in the CASP8 promoter associated with decreased risk of lung cancer. The deletion destroys a stimulatory protein 1 binding site and decreases CASP8 transcription. Biochemical analyses showed that T lymphocytes with the deletion variant had lower caspase-8 activity and activation-induced cell death upon stimulation with cancer cell antigens. Case-control analyses of 4,995 individuals with cancer and 4,972 controls in a Chinese population showed that this genetic variant is associated with reduced susceptibility to multiple cancers, including lung, esophageal, gastric, colorectal, cervical and breast cancers, acting in an allele dose-dependent manner.
17200356	Ewing Sarcoma	Promote immunity (T cell function)	Although all tested Ewing sarcoma cell lines expressed cFLIP, resistance to CD95/Fas-mediated apoptosis was only observed in two cell lines lacking caspase-8 expression.

Summary
Symbol	CASP8
Name	caspase 8, apoptosis-related cysteine peptidase
Aliases	MCH5; MACH; FLICE; Casp-8; caspase 8, apoptosis-related cysteine protease; ALPS2B; CAP4; FADD-homologous ICE ......
Chromosomal Location	2q33-q34
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 CASP8 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	Second most enriched score: 0.82	Sensitive to T cell-mediated killing
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	CASP8
Name	caspase 8, apoptosis-related cysteine peptidase
Aliases	MCH5; MACH; FLICE; Casp-8; caspase 8, apoptosis-related cysteine protease; ALPS2B; CAP4; FADD-homologous ICE ......
Chromosomal Location	2q33-q34
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 CASP8 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	0.186	0.535
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.003	0.998
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.334	0.74
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.166	0.525
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.437	0.796
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.177	0.934
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.001	0.998
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.249	0.858
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.23	0.886
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.703	0.63
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	1.465	0.511
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.14	0.0616

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of CASP8 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	4.5	0	4.5	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	CASP8
Name	caspase 8, apoptosis-related cysteine peptidase
Aliases	MCH5; MACH; FLICE; Casp-8; caspase 8, apoptosis-related cysteine protease; ALPS2B; CAP4; FADD-homologous ICE ......
Chromosomal Location	2q33-q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of CASP8. 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	CASP8
Name	caspase 8, apoptosis-related cysteine peptidase
Aliases	MCH5; MACH; FLICE; Casp-8; caspase 8, apoptosis-related cysteine protease; ALPS2B; CAP4; FADD-homologous ICE ......
Chromosomal Location	2q33-q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of CASP8. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by CASP8. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	CASP8
Name	caspase 8, apoptosis-related cysteine peptidase
Aliases	MCH5; MACH; FLICE; Casp-8; caspase 8, apoptosis-related cysteine protease; ALPS2B; CAP4; FADD-homologous ICE ......
Chromosomal Location	2q33-q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of CASP8. 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	CASP8
Name	caspase 8, apoptosis-related cysteine peptidase
Aliases	MCH5; MACH; FLICE; Casp-8; caspase 8, apoptosis-related cysteine protease; ALPS2B; CAP4; FADD-homologous ICE ......
Chromosomal Location	2q33-q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of CASP8 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	CASP8
Name	caspase 8, apoptosis-related cysteine peptidase
Aliases	MCH5; MACH; FLICE; Casp-8; caspase 8, apoptosis-related cysteine protease; ALPS2B; CAP4; FADD-homologous ICE ......
Chromosomal Location	2q33-q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between CASP8 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	CASP8
Name	caspase 8, apoptosis-related cysteine peptidase
Aliases	MCH5; MACH; FLICE; Casp-8; caspase 8, apoptosis-related cysteine protease; ALPS2B; CAP4; FADD-homologous ICE ......
Chromosomal Location	2q33-q34
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting CASP8 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting CASP8.

ID	Name	Drug Type	Targets	#Targets
DB12651	Bardoxolone	Small Molecule	CASP8	1

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