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 deficiency is associated with reduced demethylation

4 ICOS expression was significantly up-regulated on T cell

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 henotypes, they were dominated by activated (ICOS(+)PD-1(+)) and early memory precursor (CCR7(+)CD127

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

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

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

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

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

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

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

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

27 verall, these results suggest that IL-10 and ICOS differentially regulate T cell responses in the bra

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

29 Induction of IL-21 and ICOS on Ag.pTfh cells are negatively affected by both ag

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

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

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

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

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

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

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

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

38 of costimulatory molecules CD40L, CD28, and ICOS on the T cells.

39 rtion of activated cells expressing CD38 and ICOS and was associated with decreased expression of gen

40 s correlated with high expression of CD4 and ICOS in the stromal compartment of the same tumors.

41 emonstrate selective enrichment of CD40L and ICOS in SE in response to addition of CD40 and ICOSL, re

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

43 ively depend upon mitochondrial dynamics and ICOS-mTORC2 signaling.

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

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

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

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

48 AM10 on B cells in regulating both ICOSL and ICOS in a mouse model of increased humoral immunity usin

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

50 -alpha, IFN-gamma, VCAM-1, ICAM-1, PD-L1 and ICOS-L.

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

52 uggesting recent GC activity (CD38, PD1, and ICOS).

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

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

55 y unrecognized function for IL-33, Tph1, and ICOS in promoting inflammatory ILC2 responses and type 2

56 exposed for 5 weeks and co-administered anti-ICOS Ligand-targeted antibodies, three times a week for

57 that can be imaged by radiolabeling an anti-ICOS antibody and performing PET scanning.

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

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

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

61 aling is absolutely required for appropriate ICOS expression in Tfh cells and provides a competitive

62 ssed several costimulatory molecules such as ICOS and CD28.

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

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

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

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

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

68 Blocking ICOS resulted in relocation of fully developed TFH cells

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

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

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

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

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

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

75 ogical synapse (HLA-DRA, CD40LG, CD3E, CD28, ICOS) was quantified in blood from 101 surgical patients

76 The corolla captured engaged CD28, ICOS, CD226 and SLAM-F1 co-stimulators.

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

78 1(+), but then transitioned to become CD38(+)ICOS(-)PD1(+) and CD38(-)ICOS(-)PD1(+) before coming to

79 T cells are derived from the CXCR5(+)CD38(+)ICOS(+)PD1(+) subset, the subset that most resembles pre

80 licited by vaccination were initially CD38(+)ICOS(+)PD1(+), but then transitioned to become CD38(+)IC

81 S(-)PD1(+) before coming to rest as a CD38(-)ICOS(-)PD1(-) subset.

82 ed to become CD38(+)ICOS(-)PD1(+) and CD38(-)ICOS(-)PD1(+) before coming to rest as a CD38(-)ICOS(-)P

83 ific cCXCR5(+) T cells, including the CD38(-)ICOS(-)PD1(-) CXCR5(+) T cells are derived from the CXCR

84 pecific Foxp3(+) and Foxp3(-) PD1(+) CD73(+) ICOS(+) IL-10(+) peripheral regulatory T cells in predia

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

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

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

88 esidue in inducible costimulator-containing (ICOS-containing) CAR-T cells resulted in limited antitum

89 T cells, are uniquely reliant on continuous ICOS signalling to maintain their phenotype after T-cell

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

91 ired expression of inducer of costimulation (ICOS) ligand, programmed death receptor 1-ligand 1 (PD1-

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

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

94 Inducible T-cell costimulator (ICOS) is a specific marker of T-cell activation that can

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

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

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

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

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

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

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

102 eukin 21 (IL-21) and inducible costimulator (ICOS) post vaccination; these responses were strongest i

103 r, such as CTLA4 and inducible costimulator (ICOS), in the skin allograft and draining lymph nodes co

104 A(+) phenotype in an inducible costimulator (ICOS)/ICOS ligand-dependent manner.

105 t T-cell activation (inducible costimulator [ICOS]) and a broader immune phenotype with T(H)1/IFN-gam

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

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

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

109 lls and helper T cells, as well as decreased ICOS+ and 4-1BB+ natural killer cells.

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

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

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

113 on in this model is closely tied to elevated ICOS levels and decreased ICOSL levels.

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

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

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

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

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

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

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

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

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

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

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

125 ively, our results identify a novel role for ICOS costimulation in imprinting the functional stabilit

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

127 Furthermore, ICOS-Fc downmodulated hepatocyte growth factor facilitat

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

129 ands a T-cell population (CD4+CD45RO+PD-1(hi)ICOS+CCR2+CXCR5-) displaying features of recently descri

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

131 However, ICOS stimulation did not augment the antitumor activity

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

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

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

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

136 henotype in an inducible costimulator (ICOS)/ICOS ligand-dependent manner.

137 direct co-stimulatory interactions via ICOSL-ICOS.

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

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

140 ntiated memory cell population and increased ICOS and BCL6 expression was seen in HCV patients at SVR

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

142 enance requires intrinsic Bcl6 and intrinsic ICOS expression.

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

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

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

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

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

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

149 Th1)/T helper 17 (Th17) phenotype with lower ICOS and higher programmed cell death protein 1 (PD1) ex

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

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

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

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

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

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

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

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

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

159 ified that inducible costimulatory molecule (ICOS)(+) T(FH) cells and other ICOS(+) populations, incl

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

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

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

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

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

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

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

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

168 is integrated cavity output spectroscopy (OA-ICOS) technique.

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

170 tability significantly limits the ability of ICOS-deficient Treg cells to reverse ongoing inflammatio

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

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

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

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

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

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

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

178 Blockade of ICOS signalling after AAD establishment successfully dep

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

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

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

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

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

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

187 The enrichment of ICOS, CD45RO, PD-1, PDL-1, LAG-3, CTLA-4, and TIM-3 on B

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

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

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

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

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

193 highly heterogeneous in their expression of ICOS, PD1 and CD38 and the relationship between differen

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

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

196 , we demonstrated that higher frequencies of ICOS(+) T(FH) cells at baseline were associated with a p

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

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

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

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

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

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

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

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

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

206 crual with age likely through maintenance of ICOS expression.

207 the characterization of a novel mechanism of ICOS regulation.

208 Reciprocal modification of ICOS-containing CAR-T cells abolished in vivo persistenc

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

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

211 rease our understanding of the regulation of ICOS and ICOSL in the context of autoimmunity.

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

213 The role of ICOS and its ligand (ICOSL) have both been shown to be e

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

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

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

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

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

219 ontributing to IL-10 production, focusing on ICOS, a molecule implicated in IL-10 production.

220 CAR-T cells costimulated with 4-1BB or ICOS persist in xenograft models but those constructed w

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

222 ory molecule (ICOS)(+) T(FH) cells and other ICOS(+) populations, including peripheral helper T cells

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

224 s and controls the development of pathogenic ICOS(+) IFN-gamma-secreting cells.

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

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

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

228 dance relative to T(reg) predicts protective ICOS(+) PD-1(lo) CD4(+) T(conv) phenotypes and survival.

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

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

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

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

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

234 om IL-6R-cKO-infected mice exhibited reduced ICOS expression in both chimeric and nonchimeric setting

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

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

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

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

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

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

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

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

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

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

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

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

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

248 ed SE that are spatially segregated from TCR/ICOS/BST-2.

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

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

251 We propose that ICOS signaling transiently inactivates FOXO1 to initiate

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

253 We report that ICOS signaling inactivates the transcription factor FOXO

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

255 We show that ICOS deficiency does not impair induction of IL-10 by in

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

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 The ICOS pathway has been implicated in the development and

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

261 ell as inhibition of the CD40 ligand and the ICOS ligand suppressed DSA production and prevented AMR.

262 are crucial in the regulation of AAD and the ICOS/ICOS-L pathway could represent a novel therapeutic

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

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

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

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

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

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

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

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

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

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

273 We examined the possible involvement of the ICOS pathway in the accumulation of murine colonic Foxp3

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

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

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

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

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

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

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

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

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:ICOS-ligand signaling pathway is critically involve

288 correlated better with mRNA for CD30, TNFR2, ICOS, CCR4, and CD200R1 than for CRTH2.

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

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

291 Unexpectedly, ICOS ligand (ICOSL) blockade led to a local expansion of

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

293 via a Rab5-ZFYVE21-NIK axis and upregulates ICOS-L (inducible costimulator ligand) and PD-L2 (progra

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