ライフサイエンスコーパス: exhaustion

1 eed, poor appetite, physical inactivity, and exhaustion.

2 nsition to the second state is necessary for exhaustion.

3 ll activation and improves markers of immune exhaustion.

4 mitochondrial dysfunction and the resultant exhaustion.

5 xpression of the TIM3 gene related to T cell exhaustion.

6 transcription factors associated with T cell exhaustion.

7 creasingly hypo-functional, a state known as exhaustion.

8 to insufficient H60 presentation and T cell exhaustion.

9 e factors do not appear to determine time to exhaustion.

10 uce viral antigens and induce chronic immune exhaustion.

11 ith no loss of CAR cytotoxicity or increased exhaustion.

12 on and the progressive development of T cell exhaustion.

13 hat mitochondrial deregulation caused T cell exhaustion.

14 , antigen sensitivity, and susceptibility to exhaustion.

15 anscriptional program associated with T cell exhaustion.

16 in these plaques presented markers of T cell exhaustion.

17 ell as with an increase in markers of T cell exhaustion.

18 ed better for quality than those obtained by exhaustion.

19 ated C, even at expense of root death from C exhaustion.

20 ithout reversing biologic features of T-cell exhaustion.

21 wnregulation, PD-L1 upregulation, and T-cell exhaustion.

22 for pathogen control while preventing immune exhaustion.

23 omoting fratricide T cell killing and T cell exhaustion.

24 y for maintenance processes following carbon exhaustion.

25 employed to prevent the CD8(+) T cells from exhaustion.

26 massively reduced T-cell subset skewing and exhaustion.

27 sed markers of chronic T cell activation and exhaustion.

28 ads to a state of diminished function termed exhaustion.

29 activate cytolytic T cells due to persistent exhaustion.

30 ivation in the trigeminal ganglia, or T-cell exhaustion.

31 e, chronic immune activation leads to T-cell exhaustion.

32 eness, tumor regression, and prevents T cell exhaustion.

33 nses during Plasmodium-induced CD4(+) T cell exhaustion.

34 old" tumor model, instead of rescuing T cell exhaustion.

35 austion developmental trajectory to terminal exhaustion.

36 and (iii) inducing ligands that drive T cell exhaustion.

37 dministered to reverse PD-1-dependent immune exhaustion.

38 ration, and trafficking and in CD8(+) T cell exhaustion.

39 ration and upregulate genes linked to T cell exhaustion.

40 arly in severe cases, potentially suggesting exhaustion.

41 ecular regulatory interactions that underpin exhaustion.

42 ll recognition of leukemia cells intensifies exhaustion.

43 T-cell metabolic changes precede functional exhaustion.

44 itionally been associated with CD8(+) T cell exhaustion.

45 r one-legged knee-extensor exercise to local exhaustion (~2.5 h) and another day without exercise.

46 ling CAR, which induces hallmark features of exhaustion(6).

47 Strong T cell activation drives exhaustion(9,10), which may be accentuated by the redund

48 monocytes(5,6), lymphopenia(7,8) and T cell exhaustion(9,10).

49 amount of consumption, but even after patch exhaustion a prominent background signal remains, which

50 of T cell dysfunction that is distinct from exhaustion, a key strategy used by malignant tumors to e

51 in telomere maintenance result in stem cell exhaustion and a spectrum of telomere biology diseases.

52 T cell exhaustion and a suppressive bone marrow microenvironmen

53 flow cytometry revealed a downregulation of exhaustion and activation markers and an upregulation of

54 Measures of well-being including physical exhaustion and alertness were improved in faculty and fe

55 nce, deregulated nutrient sensing, stem cell exhaustion and altered intercellular communication.

56 ylation programming as a regulator of T cell exhaustion and barrier of ICB-mediated T cell rejuvenati

57 gram that governs intratumoral CD8(+) T cell exhaustion and CD4(+) T follicular helper cell developme

58 utant intestinal organoids through stem cell exhaustion and collective terminal differentiation.

59 on and increased stem cell proliferation and exhaustion and culminating in bone marrow failure.

60 Emotional exhaustion and depersonalization were reported by 28.0%

61 binding of ACE2 and SARS-CoV-2 leads to the exhaustion and down-regulation of ACE2.

62 Ameliorating T cell exhaustion and enhancing effector function are promising

63 the present worldwide issues of fossil fuel exhaustion and environmental pollution.

64 evelop a molecular signature consistent with exhaustion and failure to participate in antimicrobial d

65 ze significant energy resources and overcome exhaustion and fear.

66 ngle amino acid residue in CD28 drove T cell exhaustion and hindered the persistence of CD28-based CA

67 rinsic and extrinsic factors contributing to exhaustion and how this knowledge may inform therapeutic

68 ntial to reverse the epigenetic programme of exhaustion and how this might affect the persistence of

69 escribe a promising strategy to limit T cell exhaustion and improve persistence by changing a single

70 PD-1 blockade diminishes exhaustion and improves GVL, while blockade of Tim-3, TI

71 reases of several cellular markers of immune exhaustion and in a modest but significant improvement i

72 s associated with premature immunosenescence/exhaustion and increased susceptibility to reactivation-

73 mammary epithelial stem cell quiescence and exhaustion and is necessary for long-term maintenance of

74 se the need for detailed knowledge of T-cell exhaustion and possible interactions.

75 tion, as measured by markers associated with exhaustion and regulatory T cells, was explored by flow

76 lly stimulated and reach the effector stage, exhaustion and senescence can limit excessive inflammati

77 PA pathway with ssDNA substrate, causing RPA exhaustion and senescence.

78 ey role of TICAM2 in facilitating neutrophil exhaustion and that targeting TICAM2 may be a potential

79 However, the combination of CTL exhaustion and the ability of HIV-1 to rapidly establish

80 nto memory CD8(+) T cell differentiation and exhaustion and the association of these differentiation

81 TLs) may not be adequate because of cellular exhaustion and the evolution of CTL-resistant viruses.

82 roenvironment associated with activation and exhaustion and their spatial relationships are described

83 d host environment, and expressed markers of exhaustion and tissue homing.

84 mmarize the emerging roles of mTOR in T-cell exhaustion and transdifferentiation.

85 codes HPK1) correlates with increased T cell exhaustion and with worse patient survival in several ca

86 speed, poor grip strength, weight loss, and exhaustion) and disability (two or more difficulties in

87 btaining the ice juices (cryo-extraction and exhaustion) and the year of harvest have been evaluated.

88 3 (sTIM-3) (markers of T-cell activation and exhaustion), and sCD14 and sCD163 (markers of monocyte/m

89 mune response, but terminal differentiation, exhaustion, and apoptosis in the activated effector T ce

90 atively resistant to cellular senescence and exhaustion, and are capable of switching between cell cy

91 kness, low physical activity, shrinking, and exhaustion, and frailty evaluation is an important tool

92 tution, we studied immune activation, immune exhaustion, and HIV- and copathogen-specific T-cell resp

93 invoked a sense of not belonging, emotional exhaustion, and interfered with patient communication.

94 lking speed, low grip strength, weight loss, exhaustion, and low physical activity.

95 er measured expression of activation, immune exhaustion, and memory phenotype markers and studied pro

96 em cell fates; the former leads to stem cell exhaustion, and the latter leads to breaches of mesoderm

97 activation can be a driving force in immune exhaustion, and type I interferons (IFN-I) are emerging

98 PD-1-targeted therapies reverse TCD8 exhaustion/anergy.

99 angiogenesis, immune-suppression and T cell exhaustion are closely correlated with the poor patient

100 Emerging insights into the mechanisms of exhaustion are informing immunotherapies for cancer and

101 T cell senescence and exhaustion are major barriers to successful cancer immun

102 ently, the possibilities of interfering with exhaustion are numerous.

103 However, the mechanisms of CD4(+) T cell exhaustion are still poorly understood.

104 Importantly, IL-12 preconditioning prevented exhaustion as LAG-3, PD-1, and TOX were decreased while

105 exhibited reduced T cell differentiation and exhaustion as well as increased skewing toward Th17 cell

106 establish latency, reactivation, and immune exhaustion as well as induce the expression of caspase 3

107 is involved in the generation of neutrophil exhaustion, as TICAM2 deficient neutrophils have the dec

108 Moreover, these exhaustion-associated DNA-methylation programs were acqu

109 tion of cells expressing the senescence- and exhaustion-associated markers CD57 and PD-1.

110 g several inhibitory receptor expression and exhaustion-associated transcriptomic signature of CD8(+)

111 exercise before completing a maximal test to exhaustion at sea level (SL; 344 m) and after 5-10 days

112 anism that may contribute to terminal T cell exhaustion at the cost of memory differentiation in wild

113 itochondrial oxidative capacity, run time to exhaustion at various intensities was impaired in the KO

114 by an increase of CD8 T-cell activation and exhaustion before LoC.

115 TOX in driving the epigenetic enforcement of exhaustion, but key questions remain about the potential

116 ation is poorly understood in the context of exhaustion, but targeting effector programs may provide

117 iming promotes molecular pathways that limit exhaustion by channeling metabolic processes essential f

118 d cooperatively promoted intratumoral T cell exhaustion by modulating several inhibitory receptor exp

119 targeting pathways that induce memory T cell exhaustion can promote allograft tolerance.

120 T-cell exhaustion (CD8(+ )PD-1(+)/CTLA-4(+)) and treatment-indu

121 chromatin accessibility specific for T-cell exhaustion, characterized by enrichment for consensus bi

122 n stimulation, however, can cause CD8 T-cell exhaustion, compromising effector function.

123 ervention to reinvigorate neurogenesis whose exhaustion contributes to the waning of olfaction with a

124 equencing of NP396-specific TCRs showed that exhaustion corresponds with a significantly reduced NP39

125 domains; weight loss, low physical activity, exhaustion, decreased grip strength, and slow gait speed

126 ctivation (defined as HLA-DR+CD38+ T cells), exhaustion (define as PD-1+ T cells), and senescence (de

127 ime (isotime, p = 0.009), but was similar at exhaustion (DeltaIC(CLE) : -0.38 +/- 0.10 versus DeltaIC

128 use upregulation of CD8 or markers of T cell exhaustion despite their having similar levels of latenc

129 an impaired ability to progress through the exhaustion developmental trajectory to terminal exhausti

130 Hence, T cell exhaustion develops in the presence of abundant antigen

131 s increased single-strand DNA formation, RPA exhaustion, DNA breaks, and aberrant DNA repair intermed

132 llenged by working in a totally new context, exhaustion due to heavy workloads and protective gear, t

133 uscle oxygenation, blood lactate and time to exhaustion during (a) interval exercise (IE) consisting

134 D-1, CTLA-4, and IL-27 blocked CD4(+) T cell exhaustion during malaria infection and was associated w

135 ot directly underpin Ag-expTh1 cell loss and exhaustion during malaria infection.

136 w that Ag-experienced (Ag-exp) CD4(+) T cell exhaustion during Plasmodium yoelii nonlethal infection

137 ese findings confirm antiviral CD8(+) T cell exhaustion during SYMP herpes infection and pave the way

138 ophagy, mitochondrial dysfunction, stem cell exhaustion, epigenetic changes, abnormal microRNA profil

139 taffs that are at risk of mental of physical exhaustion, especially with the constant surge of admitt

140 dothelial cells (HUVEC, HAEC) by replicative exhaustion, exposure to ionizing radiation or doxorubici

141 ssion was associated with reversal of T-cell exhaustion features including reduced programmed cell de

142 nderstanding the features of and pathways to exhaustion has crucial implications for the success of c

143 We also performed activation/exhaustion immunophenotyping on peripheral blood mononuc

144 sengagement from HCV, whereas virus-specific exhaustion imparts a durable inhibitory imprint on cell

145 ted to a novel T cell population, and T cell exhaustion in a progressing chronic infection.

146 At exhaustion in both protocols, the vastus lateralis and i

147 T-cell exhaustion in cancer is linked to poor clinical outcomes

148 elomere therapeutics to counteract stem cell exhaustion in DC, PF, and possibly other aging-related d

149 C function in FA patients and contributes to exhaustion in FA bone marrow.

150 dy A5308 found reduced T-cell activation and exhaustion in human immunodeficiency virus (HIV) control

151 To investigate the biology of exhaustion in human T cells expressing CAR receptors, we

152 promotes adhesion and signaling and counters exhaustion in human T cells.

153 t EOMES+ SSCs are lost through proliferative exhaustion in Plzf (lu/lu) mice.

154 inoculum size, the evolutionary advantage of exhaustion in preventing lethal pathology, the ability o

155 ts inflammatory insults that underlie immune exhaustion in RMs.

156 ctivator protein-1 (AP-1), and T cell anergy/exhaustion in the absence of AP-1.

157 mains unknown what other forces drive T cell exhaustion in the tumor microenvironment (TME).

158 Tim-3 as a marker of activation rather than exhaustion in this model, and we provide additional evid

159 contributing to the development of metabolic exhaustion in TIL.

160 ff) and T(mem) cells, but it is critical for exhaustion: in the absence of TOX, T(ex) cells do not fo

161 ced epigenetic reprogramming toward terminal exhaustion, indicating that mitochondrial deregulation c

162 HIV-mediated T-cell exhaustion influences the patient's disease progression,

163 Tissue stem cell exhaustion is a key hallmark of aging, and in this study

164 CD8(+) T cell exhaustion is a major barrier to current anti-cancer imm

165 CD8(+) T cell exhaustion is a state of dysfunction acquired in chronic

166 h cancer(1-3), but dysfunction due to T cell exhaustion is an important barrier to progress(4-6).

167 onal state are termed "exhausted" and T cell exhaustion is associated with inefficient control of inf

168 on of HLA-mediated protection and CD8 T-cell exhaustion is less well characterized.

169 T cell exhaustion is marked by inhibitory molecule upregulation

170 Furthermore, we provide evidence that immune exhaustion is not caused by the antiapoptotic activity o

171 However, the mechanism of neutrophil exhaustion is not well understood.

172 t the following: 1) MAIT cell activation and exhaustion is uncoupled from the hallmark depletion of M

173 'T cell exhaustion' is a broad term that has been used to descri

174 CD4(+) T cell functional inhibition (exhaustion) is a hallmark of malaria and correlates with

175 ten associated with CD8(+) T cell functional exhaustion) is not upregulated on impaired cells but ins

176 is often compromised in cancer, where T cell exhaustion leads to loss of memory precursors.

177 lood droplets have a signature revealing the exhaustion level of the person, and discloses an entirel

178 We show for the first time an acute T-cell exhaustion-like phenomenon following an initial inflamma

179 w disease progression was associated with an exhaustion-like profile, with expression of multiple inh

180 Irreversible T cell exhaustion limits the efficacy of programmed cell death

181 ction of histone acetylation at effector and exhaustion loci, which in turn produces CD8(+) T cells w

182 lty-related phenotype criteria (weight loss, exhaustion, low activity, slowness) at >/=2 visits, or a

183 ned as >= 3 of the following: low lean mass, exhaustion, low energy expenditure, walking limitations,

184 n preceded the overt establishment of T cell exhaustion, making this signature a prime target in the

185 tion, equal differentiation, senescence, and exhaustion marker expression and were negative for regul

186 , cytolytic activity score (CYT), and T-cell exhaustion marker expression were significantly elevated

187 kin-10 production and the increase of a cell exhaustion marker expression, programmed cell death 1 re

188 V-driven immune activation, decreased T cell exhaustion marker expression, restored HIV-specific CD8

189 that emerged in these chimeras expressed the exhaustion marker PD1 and responded poorly to a strong g

190 T cells precludes it from being a bona fide exhaustion marker.

191 , which express low levels of PD-1 and TIM-3 exhaustion markers and were localized to healed sites of

192 here were also significant associations with exhaustion markers FoxP3(+), PD-1(+), and PD-L1(+) (all

193 activity, as well as decreased expression of exhaustion markers in CD4(+) and CD8(+) T cells followin

194 , including the suppression of IL-21-induced exhaustion markers LAG3, PD1, 2B4, and TIM3.

195 l memory including reduced expression of the exhaustion markers PD-1 and LAG-3 on these cells and inc

196 otype characterized by downregulation of the exhaustion markers PD-1 and LAG-3.

197 ere associated with expression of the T cell exhaustion markers PD-1 and TIM-3.

198 n and increased expression of activation and exhaustion markers preceding the abrupt loss of viral co

199 ulated with the same peptide tend to express exhaustion markers such as PD-1 or LAG-3.

200 e displayed increased NK cell activation and exhaustion markers that normalized after therapy.

201 central memory phenotype and lower levels of exhaustion markers, and display robust proliferative cap

202 l deletion of Runx induces the expression of exhaustion markers, such as IL-10 and TIGIT, on ILC2s.

203 g adoptive transfer, the rapid expression of exhaustion markers.

204 ll killing, while expressing lower levels of exhaustion markers.

205 regulation of CTLA-4 in the absence of other exhaustion markers; inhibiting CTLA-4 with a nondepletin

206 tumor infiltrating CD8+ T cells expressing "exhaustion" markers, yet oHSV infection led to a reducti

207 Chronic exhaustion may be mediated by changes in the bone marrow

208 Thus, exhaustion may not be in the human B cell's vocabulary,

209 Neutrophil exhaustion may play a key role during the establishment

210 rticle, 18 experts in the field tell us what exhaustion means to them, ranging from complete lack of

211 sustained TCR signaling can result in T cell exhaustion mediated in part by expression of programmed

212 an those obtained by the cryo-extraction and exhaustion methods.

213 sfunction, as marked by expression of T cell exhaustion molecules, and posttransplant infections in a

214 f transplant, we investigated whether T cell exhaustion occurs and has a role in determining transpla

215 Collagen-induced T cell exhaustion occurs through the receptor LAIR1, which is u

216 This phenotype, known as T cell exhaustion, occurs during chronic infections caused by a

217 t small tail skins (0.8 cm x 0.8 cm), led to exhaustion of anti-male tetramer(+) CD8(+) T cells and s

218 ade the hosts' immune system by inducing the exhaustion of antiviral T cells.

219 Exhaustion of aspartate in these cells resulted in immed

220 granules, and Q-bodies, is triggered by the exhaustion of ATP.

221 -limited encounter between proteins, and the exhaustion of available valencies within smaller cluster

222 thways of proteostasis derailment, including exhaustion of cardioprotective heat shock proteins, disr

223 , increasing tumor bacterial load, promoting exhaustion of CD8(+) T cells, and overactivating DCs, le

224 L-10 and IL-35 in promoting BLIMP1-dependent exhaustion of CD8(+) TILs that limits effective anti-tum

225 warming below 1.5-2 degrees C will avoid the exhaustion of excess carbonate in the Northeast Atlantic

226 production is not the result of the complete exhaustion of exploitable copper but of the combination

227 abolic network does not solely depend on the exhaustion of glucose.

228 Exhaustion of Hepatitis C Virus (HCV)-specific T cells a

229 reproduced by incorporating usage-dependent exhaustion of inhibition in an adaptive neural network t

230 aling that BMP signaling inactivation causes exhaustion of lipid reserves in somatic tissues.

231 Exhaustion of T cells limits their ability to clear chro

232 ntestinal epithelial cells and proliferative exhaustion of the intestinal stem cell compartment compa

233 njection of cobra venom factor, resulting in exhaustion of the maternal complement component C3.

234 Here, we show that exhaustion of the metabolic inputs that couple carbon ca

235 itro, indicating a possible low frequency or exhaustion of the precursor population.

236 hat distracts cell division mode, leading to exhaustion of the progenitor pool.

237 enewal, loss of cell identity, and premature exhaustion of the quiescent satellite cell pool.

238 gle-item questions of experiencing emotional exhaustion or depersonalization.

239 This process, known as T cell exhaustion or dysfunction(1), is manifested by epigeneti

240 ing levels of cells indicating either T-cell exhaustion or systemic immunosuppression may be markers

241 ts rendered senescent by stress, replicative exhaustion, or oncogene activation, mTORC1 is constituti

242 xpression revealed progression of CD8 T-cell exhaustion over the course of the infection in both pati

243 Immune senescence and exhaustion paradigms offer only partial explanations.

244 Finally, inhibition of exhaustion pathway should be considered as a new therape

245 enes and proteins associated to major T cell exhaustion pathways and were dysfunctional.

246 +) T cells identified the presence of T cell exhaustion pathways in nonresponding tumors and T cell a

247 Thus, both the PD-1 and the LAG-3 exhaustion pathways play a fundamental role in ocular he

248 Moreover, blockade of T cell exhaustion pathways restored the function of CD8(+) T ce

249 ctional CD8(+) T(EM) cells, expressing major exhaustion pathways.

250 al program, similar to but distinct from the exhaustion pattern of cells responding to chronic infect

251 in populations expressing markers of T cell exhaustion, PD-1 and TIGIT.

252 higher levels of activation (HLA-DR(+)) and exhaustion (PD1(+)) markers.

253 r mechanism by itself could fully rescue the exhaustion phenotype.

254 This 'regenerative cell exhaustion' process is intensified by increasing oxidati

255 We hypothesize that the TOX-induced exhaustion program serves to prevent the overstimulation

256 in the psoriatic cells that differed from an exhaustion program.

257 ll antitumor responses and commitment to the exhaustion program.

258 of Tox in TST cells in tumours abrogated the exhaustion program: Tox-deleted TST cells did not upregu

259 d cycle and inhibiting terminal effector and exhaustion programs, including mRNA expression of member

260 (r = -1.64; p = 0.0255) and higher emotional exhaustion (r = 0.246; p = 0.0007).

261 cular alterations reported in FA lead to HSC exhaustion remains poorly understood.

262 T cell exhaustion represents one of the most pervasive strategi

263 of a T cell: quiescence, ignorance, anergy, exhaustion, senescence and death.

264 lead to aberrant gene regulation, stem cell exhaustion, senescence, and deregulated cell/tissue home

265 PIK3CD GOF mutations aberrantly induce exhaustion, senescence, or both and impair cytotoxicity

266 rted CD8(+) T-cell prognostic expression and exhaustion signatures were only found in the original ad

267 cific murine CD8 T cells at the effector and exhaustion stages of an immune response identified progr

268 ependently assay the phenotype, specificity, exhaustion status, and lineage of single T cells.

269 0% showed evidence of severe burnout on the "exhaustion" subscale, 44% on the "depersonalization" sub

270 evated expression of markers associated with exhaustion, such as PD1 and LAG3, and regulatory CD4+FOX

271 latency reactivation, apoptosis, and immune exhaustion, suggesting that LAT and CD80 have multiple o

272 + T cells, an indicator of T-cell senescence/exhaustion that is associated with biological aging, was

273 l epigenetic and transcriptional features of exhaustion that mirror those seen in chronic viral infec

274 We now demonstrate that even during exhaustion there is a subset of functional CD8(+) T cell

275 overexpress c-Jun renders them resistant to exhaustion, thereby addressing a major barrier to progre

276 ions and cause hematopoietic stem cell (HSC) exhaustion; therefore, IFN-I expression must be tightly

277 restraining T cell senescence and functional exhaustion through epigenetic silencing of drivers of te

278 augments immune function yet promotes T cell exhaustion through PDL1.

279 nteraction with collagen, and induces T cell exhaustion through SHP-1.

280 LPS drives neutrophil exhaustion through TICAM2 mediated activation of Src fam

281 Occurring temporal to T cell exhaustion, thymic cellularity reconstituted despite ong

282 DeltaIC) was less during IE than CLE at CLE exhaustion time (isotime, p = 0.009), but was similar at

283 A broader approach to counteract immune exhaustion to alleviate complications and improve effica

284 d an incremental exercise test to volitional exhaustion to determine VO2 peak with lumbar intrathecal

285 d an incremental exercise test to volitional exhaustion to determine VO2 peak with lumbar intrathecal

286 required to prevent hematopoietic stem cell exhaustion to ensure immune homeostasis.

287 hat express the transcriptional regulator of exhaustion TOX, and expanding the pool of stem-like TCF1

288 of SFK inhibitor Dasatinib blocks neutrophil exhaustion triggered by the prolonged LPS challenge.

289 immune evasion that is independent of T-cell exhaustion, using B-cell-specific deletion of the transc

290 e (P = 0.008), and a signature of CD8 T cell exhaustion was associated (q = 2.8 x 10(-149)) with a po

291 Exhaustion was associated with a profound defect in the

292 This reversal of CD8(+) T-cell exhaustion was dependent on both agonistic GITR signalin

293 Emotional exhaustion was higher among women (beta 2.933; p = 0.023

294 To study CD4(+) T cell exhaustion, we used the TCR-transgenic B6 TEa cells that

295 CD4+ and CD8+ T-cell exhaustion were independently associated with a higher c

296 of CD30 and markers of T-cell activation and exhaustion were performed along with HIV-1 RNA and deoxy

297 emic parasite control associated with immune exhaustion, which was reversible in part by blocking PD-

298 Reversing immune exhaustion with an anti-PD-L1 antibody may improve human

299 development, therapeutic reversal of immune-exhaustion with immune checkpoint inhibitors (ICPIs) has

300 eranged interferon response, profound immune exhaustion with skewed T cell receptor repertoire and br