ライフサイエンスコーパス: ICOS

1 ICOS and HLA-DR activation were significantly higher in

2 ICOS contributed to Treg maintenance in aged mice, becau

3 ICOS expression was significantly up-regulated on T cell

4 ICOS functions as an essential immune regulator and ICOS

5 ICOS is a T-cell coregulatory receptor that provides a c

6 ICOS is prominently expressed on T follicular helper (TF

7 ICOS regulates CD4(+) T cell activation and promotes the

8 ICOS signaling provided critical support for the effecto

9 ICOS stimulates T follicular helper cell differentiation

10 ICOS(+) Tregs were the most proliferative lymphocyte pop

11 ICOS, a member of the CD28 family, represents a key mole

12 ICOS-Fc specifically inhibited the migration of HUVECs,

13 nstrate that the frequency of CXCR5(+)PD-1(+)ICOS(+)-activated circulating Tfh cells is increased bot

14 on of the master transcription factor Bcl-6, ICOS co-stimulation was essential to maintain the phenot

15 ding the T(H)17 cell-promoting factors IL-6, ICOS, c-Rel, IRF4, IkappaBNS and IkappaBzeta.

16 These Tregs comprised activated ICOS(+) Tregs that were able to suppress not only conven

17 In contrast, activated ICOS(hi) PD-1(hi) circulating T follicular helper (Tfh)

18 In contrast, the provision of additional ICOS signaling through direct ICOS-L expression by tumor

19 ng a blocking, nondepleting antibody against ICOS ligand (ICOS-L).

20 nd in lupus models, was also increased in an ICOS-dependent manner in Sle1 mice and correlated with a

21 ast, anti-CTLA-4 induces the expansion of an ICOS(+) Th1-like CD4 effector population in addition to

22 Although Tc17 cells activated with an ICOS agonist cosecreted heightened IL-17A, IL-9, and IFN

23 Conversely, activating Tc17 cells with an ICOS agonist in vitro enhanced their capacity to eradica

24 ct on antitumor Tc17 cells activated with an ICOS agonist.

25 In addition, T cells redirected with an ICOS-based CAR maintained a core molecular signature cha

26 nscriptional complex that binds in IL-10 and ICOS promoter elements and controls gene expression in h

27 ells had lower expression of Maf, IL-21, and ICOS, and this was accompanied by a reduction in the pro

28 rial therapies incorporating anti-CTLA-4 and ICOS engagement.

29 The family includes CD28, CTLA-4, and ICOS as well as other proteins, including PD-1, BTLA, an

30 of high expression of B cell lymphoma 6 and ICOS.

31 fy the separable roles of delivery of Ag and ICOS-L by cognate B cells for Tfh cell maturation and fu

32 wever, the separable contributions of Ag and ICOS-L delivery by cognate B cells to Tfh cell developme

33 short isoforms adequately supported Bcl6 and ICOS expression in TFH cells, Tcf1 long isoforms remaine

34 ow show that concomitant CTLA-4 blockade and ICOS engagement by tumor cell vaccines engineered to exp

35 ing via the costimulatory receptors CD28 and ICOS but were inhibited by PD-1 and PD-L1.

36 (-/-) mice, we found that CD4(+) T cells and ICOS(+/+) T cells were required for protection against l

37 econdary responses, dependent on T cells and ICOS-dependent costimulation, and in which priming could

38 way, suggesting that both direct contact and ICOS-ICOSL interaction are important in the regulation o

39 ation of the suppressive molecules CTLA4 and ICOS to establish Treg-cell functional competency.

40 Moreover, FOXP3(+) and ICOS(+) cells are overrepresented in this CD31(-) subpop

41 ICOS on Tfh cells in and around the GC, and ICOS-ICOSL interactions were similarly crucial at late t

42 The proper regulation of ICOS and ICOS ligand (ICOSL) has been shown to be essential for m

43 ILC2s expressed both ICOS and ICOS-ligand, and the ICOS:ICOS-ligand interaction promot

44 ilencing abrogates activin-A-driven IL10 and ICOS up-regulation and impairs the suppressive functions

45 e lungs of animals surviving lung injury and ICOS(+/+) Tregs promoted survival in animals that receiv

46 ion and GVHD in an outbred animal model, and ICOS blockade may be an approach to prevention and treat

47 Thus, OX40 and ICOS act in a cooperative, nonredundant manner to maximi

48 markers expressed on GCTfh, CXCR5, PD1, and ICOS, to identify potential circulating CXCR5(+)CD4(+) T

49 dings suggest an essential role for pDCs and ICOS-L in immunosuppression mediated by ICOS(+) Foxp3(+)

50 nctions as an essential immune regulator and ICOS blockade is a potential approach to immune modulati

51 RP, Itgb8, Pglyrp1, Il1rl1, Itgae, TIGIT and ICOS are Th17-to-Treg cell transdifferentiation-associat

52 agement and was abrogated by antagonist anti-ICOS and anti-ICOSL antibodies.

53 B6.Sle1 mice, using a glyco-engineered anti-ICOS-depleting Ab, resulted in a significant reduction i

54 ICOS blockade were observed in MLR when anti-ICOS was combined with suboptimal concentrations of cyto

55 Moreover, treatment of mice with anti-ICOS ligand Abs to modulate ICOS-ICOS ligand signaling r

56 ssed several costimulatory molecules such as ICOS and CD28.

57 Whereas costimulatory receptors such as ICOS are accepted as being important for the induction o

58 of ILC2s by co-stimulatory molecules such as ICOS, regulatory T cells and by compounds such as nicoti

59 egrated cavity output spectroscopy (off-axis ICOS) to quantify ambient oxygen with a precision (1sigm

60 Therefore, the B7h-ICOS interaction may modulate the spread of cancer metas

61 ncy-associated gene variants in TACI, BAFFR, ICOS, CD21, LRBA, and CD27 as genetically dissimilar fro

62 B7h, expressed by several cell types, binds ICOS expressed by activated T cells.

63 Blocking ICOS resulted in relocation of fully developed TFH cells

64 ILC2s expressed both ICOS and ICOS-ligand, and the ICOS:ICOS-ligand interacti

65 Antitumor immunity can be improved by ICOS-targeting therapies, but their mechanism of action

66 and ICOS-L in immunosuppression mediated by ICOS(+) Foxp3(+) Treg cells, leading to tumor progressio

67 is supported after CD4(+) T cell priming by ICOS signaling.

68 have previously shown that B7h triggering by ICOS-Fc inhibits human endothelial cell adhesiveness.

69 Canine ICOS was expressed in an inducible pattern on T cells ac

70 lymphocyte activation gene 3, KLRG1, CD103, ICOS, CTLA-4, and granzyme B.

71 pressed costimulatory molecules (CD28, CD27, ICOS), and had high levels of PD-1 and coexpression of C

72 ted molecules, such as PD-L1 (B7-H1, CD274), ICOS-L (CD275), and B7-H3 (CD276).

73 shared "main response" was induced by CD28, ICOS, and, surprisingly, BTLA and CD80, with very limite

74 These receptors have both stimulatory (CD28, ICOS) and inhibitory roles (CTLA-4, PD-1, BTLA, and TIGI

75 cells (T(GC)) as lymph node-resident CD4(+) ICOS(+) CXCR4(+) CXCR5(+) PSGL-1(lo) PD-1(hi) cells.

76 Adoptive transfer of cervical LN CD4+ICOS+, but not CD4+ICOS-, cells inhibited BPEx-induced a

77 ansfer of cervical LN CD4+ICOS+, but not CD4+ICOS-, cells inhibited BPEx-induced airway hyperresponsi

78 Blockade of ICOSL rescues T cell ICOS surface expression and rescues, at least in part, T

79 induced a transient increase of circulating ICOS(+)PD-1(+)CXCR3(+) T follicular helper (cTfh) cells

80 ally in effector CD4(+) T cells by combining ICOS agonism and Treg depletion.

81 flammatory, but not tolerogenic, conditions, ICOS emerges as a pivotal effector molecule in the early

82 indirectly regulating ICOS, thus controlling ICOS/ICOSL-dependent responses.

83 ng intensity from the inducible costimulator ICOS and kinase PI(3)K by suppressing expression of the

84 Signaling via the inducible costimulator ICOS fuels the stepwise development of follicular helper

85 The inducible T cell costimulator (ICOS) is a potent promoter of organ inflammation in muri

86 ecules IL-10, inducible T-Cell costimulator (ICOS), lymphocyte activation gene 3 protein (LAG-3), and

87 40L, PD-1, and inducibl T-cell costimulator (ICOS), which may favor the accumulation of autoreactive

88 necessity of inducible T-cell costimulator (ICOS)-ICOS ligand cell contact for Treg cell-mediated IL

89 oxp3, and the inducible T cell costimulator (ICOS).

90 IL-21/IL-21R, inducible T-cell costimulator (ICOS)/ICOS ligand, and CD40L/CD40 hindered GC formation

91 ection by increasing inducible costimulator (ICOS) expression on TFH cells and reducing the number of

92 a CAR containing the inducible costimulator (ICOS) intracellular domain generates tumor-specific IL-1

93 of up-regulation of inducible costimulator (ICOS) ligand on TACI-deficient B cells, given that ablat

94 The inducible costimulator (ICOS) plays a key role in the development of Th17 cells,

95 Inducible costimulator (ICOS), a member of the CD28 family of costimulatory mole

96 We found that costimulatory ICOS-LICOS interaction between T cells and endothelial c

97 v by anti-CD3 and either anti-CD28, -CTLA4, -ICOS, -PD1, -BLA, or -CD80.

98 entified variants in IL21, IL21R, CD28/CTLA4/ICOS, CD58, ARID3A and IL16 as novel PBC risk loci.

99 abling B-cell help, including IL-21, CXCL13, ICOS, and MAF.

100 significantly higher frequencies of CXCR5(+)ICOS(+) TFH cells in autoimmune BXD2 mice, and these cel

101 levels of Tfh cell markers, including CXCR5, ICOS, PDCD1, BCL6, and IL21.

102 of additional ICOS signaling through direct ICOS-L expression by tumor cells enhanced tumor rejectio

103 the CD28 or the 4-1BB intracellular domains, ICOS signaling increased IL-17A, IL-17F, and IL-22 follo

104 regulates iNKT maturation, but downregulates ICOS expression in iNKT cells by inhibiting mTOR complex

105 te the adaptive immune response by enhancing ICOS expression on CD4(+) T cells and amplifying Th2 and

106 When this shedding is blocked, excessive ICOS internalization occurs.

107 To explore ICOS as a direct target in the tumour, we engineered a r

108 ILC2s express ICOS, a T cell costimulatory molecule with a currently u

109 by tumor cell vaccines engineered to express ICOS ligand enhanced antitumor immune responses in both

110 bodies (mAbs) against cell surface-expressed ICOS were produced and tested in vitro for suppression o

111 If expressed, ICOS did not act as a general T cell costimulator but se

112 , we engineered a recombinant NDV-expressing ICOS ligand (NDV-ICOSL).

113 erate CD25(high)FoxP3(high) Tregs expressing ICOS.

114 e clinical outcomes than patients with fewer ICOS(+) Tregs.

115 Finally, ICOS-Fc inhibited the adhesion of both immature DCs and

116 ligand signaling revealed a requirement for ICOS in TFH differentiation only after day 6 postinfecti

117 onflicting data indicating a requirement for ICOS-L expression on cognate B cells for Tfh cell develo

118 In addition, CD4(+)Foxp3 (+) ICOS(+) T cells were enriched in the lungs of animals su

119 phenotypic profiles, such as elevated FoxP3, ICOS, and CTLA-4 expression, with CTLA-4 expression stri

120 Furthermore, ICOS-Fc downmodulated hepatocyte growth factor facilitat

121 duction of multiple Treg cell markers (e.g., ICOS, PD-1, GITR) on pulmonary CD25(+) Foxp3(+) cells in

122 ), CD4(+) T cells, with increased IFN-gamma, ICOS, granzyme B and perforin expression.

123 a highly activated subpopulation of CD44(hi)ICOS(hi) intratumoral Tregs were preferentially targeted

124 exhibited a memory phenotype including high ICOS expression, increased cytokine production, and limi

125 However, ICOS stimulation did not augment the antitumor activity

126 Interestingly, however, ICOS retrogenic CD8(+) T cells also preferentially homed

127 t B7h triggering via a soluble form of ICOS (ICOS-Fc) inhibits the adhesion of polymorphonuclear and

128 sity of inducible T-cell costimulator (ICOS)-ICOS ligand cell contact for Treg cell-mediated ILC2 sup

129 IL-21R, inducible T-cell costimulator (ICOS)/ICOS ligand, and CD40L/CD40 hindered GC formation and cG

130 direct co-stimulatory interactions via ICOSL-ICOS.

131 Alteration of this motif in ICOS or depletion of TBK1 in T cells severely impaired t

132 T/B interactions and B cell help, including ICOS, PD-1, and SLAM family receptors.

133 predominance of iNKT-17 cells, and increased ICOS expression was required for the predominance of iNK

134 enance requires intrinsic Bcl6 and intrinsic ICOS expression.

135 By itself, ICOS-L blockade reduced accumulation of intratumoral T r

136 ed numbers of CD44(hi), CD62L(lo), KLRG1(+), ICOS(+) short-lived effector cells, indicating an influx

137 d Sternberg (HRS) cell-expressed CD30/OX40-L/ICOS-L, and other activation markers.

138 we demonstrate that the costimulatory ligand ICOS ligand (ICOSL) is selectively downregulated on the

139 , nondepleting antibody against ICOS ligand (ICOS-L).

140 fh) cell development, as is the ICOS ligand (ICOS-L); however, the separable contributions of Ag and

141 ereas inducible T-cell co-stimulator ligand (ICOS-L; alias B7H2) was expressed by a subset of RMSs an

142 -L2]), CD275 (inducible costimulator ligand [ICOS-L]), CD276 (B7-H3), B7-H4, and B7-H6.

143 Costimulatory molecules like ICOS are crucial in mediating T cell differentiation and

144 However, in the B16-F10-metastasized lungs, ICOS-Fc also increased IL-17A/RORc and decreased IL-10/F

145 This method, called M-ICOS, was carefully tested in a laboratory and was subse

146 The M-ICOS method allowed for the determination of dissolved m

147 ectly loaded on already matured DCs and mDCs(ICOS).

148 ed with LPS in the presence of ICOS-Fc (mDCs(ICOS)) produced greater amounts of IL-23 and IL-10, and

149 Moreover, mDCs(ICOS) pulsed with the keyhole limpet hemocyanin Ag durin

150 es and suggest a role for TRAF3 in mediating ICOS expression in Treg cells.

151 ed shedding of ICOSL on B cells and moderate ICOS internalization on T cells.

152 f mice with anti-ICOS ligand Abs to modulate ICOS-ICOS ligand signaling revealed a requirement for IC

153 Mechanistically, the costimulatory molecule ICOS activated mTORC1 and mTORC2 to drive glycolysis and

154 ned expression of the costimulatory molecule ICOS and its downstream signaling at early stages of T c

155 eractions between the costimulatory molecule ICOS and the ICOS ligand on MDDCs amplified nucleotide-b

156 Inducible co-stimulator molecule (ICOS) and HLA-DR were used to define mid- and long-term

157 levels of inducible co-stimulatory molecule (ICOS).

158 ially all other T cell-activation molecules, ICOS was found to be induced in the immunity response an

159 Moreover, ICOS-Fc downmodulated the phosphorylation of focal adhes

160 Of note, ICOS signaling also induced the expression of IFN-gamma

161 Through the creation of novel ICOS retrogenic Ag-specific TCR-transgenic CD8(+) T cell

162 OA-ICOS involves no sample conversion and has a small footp

163 OA-ICOS measurements were compared with two independent iso

164 adspace N2O was manually injected into an OA-ICOS isotopic N2O laser analyzer through a syringe septu

165 The use of OA-ICOS technology yields accurate and precise delta(15)N a

166 demonstrate the precision and accuracy of OA-ICOS: delta(18)OVSMOW-SLAP = -24.74 +/- 0.07 per thousan

167 is integrated cavity output spectrometer (OA-ICOS).

168 is integrated cavity output spectroscopy (OA-ICOS) is demonstrated for accurate and precise measureme

169 is integrated cavity output spectroscopy (OA-ICOS).

170 For all these OA-ICOS measurements, precision can be further enhanced by

171 n vitro but no differences in the ability of ICOS(-/-) Tregs to protect from lethal lung injury.

172 Here we show that selective ablation of ICOS ligand (ICOSL) in CD11c(+) cells, but not in B cell

173 P. c. chabaudi AS infection, the absence of ICOS resulted in an enhanced Th1 immune response that re

174 chabaudi AS infection, the absence of ICOS resulted in an enhanced Th1 immune response that re

175 Despite the absence of ICOS, CD4(+) T cells were capable of expressing PD-1, B

176 Here we report that activation of ICOS in CD4(+) T cells promoted interaction of the p85al

177 molecular bridge that couples activation of ICOS to Bcl-6-dependent functional differentiation of TF

178 Ab blockade of ICOS ligand, expressed by popliteal lymph node B cells,

179 Partial blockade of ICOS signalling, either by injections of low dose of ICO

180 ess high levels of ICOS, and the blockade of ICOS/ICOSL interaction prevents their expansion and amel

181 Direct comparison of ICOS(-/-) Tregs to ICOS(+/+) Tregs found defects in vitr

182 However, the contribution of ICOS and TFH cells to autoantibody profiles under pathol

183 Genetic deletion of ICOS impacted the expansion of TFH cells in B6.Sle1 mice

184 n are dependent on cognate B cell display of ICOS-L, but only when Ag presentation by the latter is l

185 This work investigated the effect of ICOS-Fc on human monocyte-derived dendritic cells (DCs).

186 m of this work was to evaluate the effect of ICOS-Fc on the migration of cancer cells and ECs.

187 Immunosuppressive effects of ICOS blockade were observed in MLR using peripheral bloo

188 Immunosuppressive effects of ICOS blockade were observed in MLR when anti-ICOS was co

189 The elimination of ICOS-expressing CD4(+) T cells in B6.Sle1 mice, using a

190 nts with melanoma with enhanced expansion of ICOS(+) Tregs in blood following the first cycle of HD I

191 regulatory T cells, inhibit the expansion of ICOS(+)IL-10(+) Tregs, inhibit TGF-beta-induced FOXP3 ex

192 differences, including reduced expression of ICOS and elevated production of IL-10 and IFNgamma, whic

193 help ability, and had greater expression of ICOS compared with young adults.

194 ge and contributed to elevated expression of ICOS on aged Tregs.

195 Expression of ICOS on CD3 cells was evaluated by flow cytometry using

196 ith the requirement for B cell expression of ICOS-L overcome by robust Ag delivery.

197 wn that B7h triggering via a soluble form of ICOS (ICOS-Fc) inhibits the adhesion of polymorphonuclea

198 gnitude of Ab responses and the frequency of ICOS(+) (inducible T-cell costimulator) Tfh-like cells i

199 d with disease activity and the frequency of ICOS(+) blood Tfh cells in SLE.

200 However, the impact of ICOS signaling on programmed differentiation is not well

201 Importantly, the increase of ICOS(+)PD-1(+)CXCR3(+) cTfh cells strongly correlated wi

202 nalyzed the correlation with the increase of ICOS(+)PD-1(+)CXCR3(+) cTfh cells.

203 toward a T-cell attack, whereas induction of ICOS-L did not.

204 In wild-type mice, interaction of ICOS/ICOSL results in ADAM10-induced shedding of ICOSL o

205 Here we showed that a lack of ICOS on murine ILC2s and blocking the ICOS:ICOS-ligand i

206 d be further characterized by high levels of ICOS and CD69.

207 These cells express high levels of ICOS, and the blockade of ICOS/ICOSL interaction prevent

208 crual with age likely through maintenance of ICOS expression.

209 the characterization of a novel mechanism of ICOS regulation.

210 tive humoral immunity, and overexpression of ICOS results in aberrant Ab production resembling lupus.

211 that DCs matured with LPS in the presence of ICOS-Fc (mDCs(ICOS)) produced greater amounts of IL-23 a

212 Here, we describe the expression profile of ICOS in dogs and determine whether ICOS expression is up

213 The proper regulation of ICOS and ICOS ligand (ICOSL) has been shown to be essent

214 bes for the first time the exclusive role of ICOS and its downstream signaling in the maintenance of

215 pus-prone mouse model to examine the role of ICOS in the expansion and function of pathogenic TFH cel

216 Here, we define the role of ICOS signaling in antitumor immunity using a blocking, n

217 we therefore sought to determine the role of ICOS signaling on CD8(+) T cell programmed differentiati

218 metastases, which suggests the novel use of ICOS-Fc as an immunomodulatory drug.

219 tion of Tfh cells with reduced dependence on ICOS ligand.

220 on of these cells were strictly dependent on ICOS-L costimulation provided by tumor plasmacytoid dend

221 ery limited CD28-specific (primarily Il2) or ICOS-specific elements (including Th1 and Th2 but not th

222 r Th1 cells, does not involve CD40, OX40, or ICOS costimulation, but does involve B7/CD28 interaction

223 It is also unknown whether other ICOS-induced processes might contribute to lupus patholo

224 and were clonally related to a resting PD1(+)ICOS(-) CD4(+) memory T cell subset.

225 ermore, an activated, antigen-specific PD1(+)ICOS(+) cTfh subset clonally expanded after booster immu

226 ting the ICOS pathway should seek to promote ICOS signaling specifically in effector CD4(+) T cells b

227 expression of the immune-checkpoint protein ICOS on T cells and induced follicular Th cell different

228 s promoted survival in animals that received ICOS(-/-) T cells.

229 ep process that depends upon the co-receptor ICOS and the activation of phosphoinositide-3 kinase lea

230 ing expression of the costimulatory receptor ICOS and promoting expression of the transcriptional rep

231 ell types express the costimulatory receptor ICOS and require the transcription factor Bcl-6 for thei

232 ignaling through the co-stimulatory receptor ICOS (inducible co-stimulator).

233 ting ICOSL, as well as indirectly regulating ICOS, thus controlling ICOS/ICOSL-dependent responses.

234 The phenotypic changes observed in B6.Sle1-ICOS-knockout mice were also associated with a significa

235 ow in this study that lineage-negative ST2(+)ICOS(+)CD45(+) type 2 ILCs and CD4(+) T cells can potent

236 recently identified inducible co-stimulator (ICOS) as a crucial player in the antitumor effects of CT

237 receptors, with the inducible co-stimulator (ICOS) being most notable.

238 activation, inducible T-cell co-stimulator (ICOS) expression and interleukin-21 (IL-21) cytokine sec

239 o increased CD3 and inducible co-stimulator (ICOS) expression on T cells.

240 Tfh-cell-promoting inducible co-stimulator (ICOS) ligand.

241 level expression of inducible co-stimulator (ICOS), which in turn was required for TFR cell generatio

242 The co-stimulators ICOS (inducible T cell co-stimulator) and CD28 are both

243 Collectively, these data suggest ICOS is not required for TFH induction during P. c.

244 ram is induced following early and sustained ICOS expression, resulting in the generation of more cyt

245 (+) T cells that receive early and sustained ICOS signaling during Ag exposure.

246 This study demonstrates that ICOS but not CXCR5 marks T cells with B helper activity

247 We found that ICOS costimulation was important for the functional main

248 Our results indicate that ICOS regulates the ontogeny and homeostasis of B6.Sle1 T

249 We propose that ICOS signaling transiently inactivates FOXO1 to initiate

250 We propose that ICOS(+)PD-1(+)CXCR3(+) Tfh cells directly contribute to

251 We report that ICOS signaling inactivates the transcription factor FOXO

252 Additional investigation revealed that ICOS stimulation not only increased IL-2Ralpha, CXCR3, a

253 We show that ICOS expression discriminates effector Foxp3(-) T cells

254 Taken together, our results showed that ICOS signaling during antitumor responses acts on both T

255 These data suggest that ICOS affects Treg development but is not necessarily req

256 These studies suggest that ICOS plays a role in graft rejection and GVHD in an outb

257 ell lines to HUVECs; thus, we suggested that ICOS-Fc may act as an anti-inflammatory and antitumor ag

258 The ICOS is not expressed on resting T cells but is rapidly

259 ween the costimulatory molecule ICOS and the ICOS ligand on MDDCs amplified nucleotide-binding oligom

260 expressed both ICOS and ICOS-ligand, and the ICOS:ICOS-ligand interaction promoted cytokine productio

261 Blocking the ICOS pathway using an antagonist mAb or by using recipie

262 -germinal center B-cell axis by blocking the ICOS-ICOSL pathway reduced the development of atheroscle

263 ack of ICOS on murine ILC2s and blocking the ICOS:ICOS-ligand interaction in human ILC2s reduced AHR

264 r CD8(+) T cells in immune regulation by the ICOS-B7h pathway.

265 factor Bcl-6 for their differentiation, the ICOS-dependent pathways that coordinate their responses

266 ection of TH17 cells with a CAR encoding the ICOS intracellular domain is a promising approach to aug

267 recipient mice genetically deficient in the ICOS ligand reduced the antitumor activity of adoptively

268 direct cellular contact or by inhibiting the ICOS-ICOS-ligand (ICOSL) pathway, suggesting that both d

269 licular Th (Tfh) cell development, as is the ICOS ligand (ICOS-L); however, the separable contributio

270 cells partially resistant to blockade of the ICOS ligand (ICOSL) during T(FH) cell development.

271 Notably, abrogation of the ICOS pathway in NOD neonates or BDC2.5-NOD (BDC2.5) mice

272 ells express B7h, which is the ligand of the ICOS T cell costimulatory molecule.

273 data suggest that increased expansion of the ICOS(+) Treg population following the first cycle of HD

274 verall, we propose a novel regulation of the ICOS/ICOSL axis, with ADAM10 playing a direct role in re

275 novel view on the use of interactors of the ICOS:B7h system as immunomodulatory drugs.

276 st that vaccination strategies targeting the ICOS and Bcl6 pathways in CD4 T cells may provide new av

277 Thus, effective therapies targeting the ICOS pathway should seek to promote ICOS signaling speci

278 Therapies targeting the ICOS signaling pathway may offer new opportunities for t

279 pathogenesis and suggest that targeting the ICOS/ICOSL pathway may be a promising immunotherapy for

280 Collectively, our work reveals that the ICOS pathway potentiates the antitumor activity of adopt

281 Here we report that the ICOS-B7h costimulatory pathway plays a critical role in

282 and have implications for using therapeutic ICOS blockade in settings of abundantly available Ag, su

283 Our results reveal that these ICOS signals critically impacted cell fate decisions of

284 cell-expressed messenger RNAs, and of these, ICOS is the most strongly cell autonomously upregulated

285 1 inhibited Tfh cell development even though ICOS was overexpressed.

286 Positive regulation of ILC-2s through ICOS has been recently elucidated.

287 Thus, ICOS strongly contributed to the dramatic change in the

288 Thus, ICOS:ICOS-ligand signaling pathway is critically involve

289 How ICOSL is regulated in response to ICOS interaction is still unclear.

290 Direct comparison of ICOS(-/-) Tregs to ICOS(+/+) Tregs found defects in vitro but no difference

291 However, a signaling pathway unique to ICOS has not been identified.

292 These results reveal a previously unknown ICOS-TBK1 signaling pathway that specifies the commitmen

293 rofile of ICOS in dogs and determine whether ICOS expression is up-regulated during chronic graft-ver

294 nd here that the kinase TBK1 associated with ICOS via a conserved motif, IProx, that shares homology

295 Treg generation was associated with ICOS/ICOSL engagement and was abrogated by antagonist an

296 Interestingly, OX40 was coexpressed with ICOS on Tfh cells in and around the GC, and ICOS-ICOSL i

297 r T cell (Teff) responses, was impaired with ICOS-L blockade.

298 tumors, TH17 cells that were redirected with ICOS-based CARs mediated efficient antitumor responses a

299 motif abolished the association of TBK1 with ICOS, TRAF2 and TRAF3, which identified a TBK1-binding c

300 Finally, treatment with ICOS-Fc inhibited the development of lung metastases upo