UNASSIGNED: @entity204 ( @entity204 ) is a well-established instigator of 'anti- @entity5 vaccination-effect (AVE)'. @entity204 has shown considerable preclinical promise, yet there remain subset of @entity5 @entity1 that fail to respond to clinically-applied @entity204 inducers. Non-responsiveness to @entity204 inducers could be explained by the existence of @entity5 cell-autonomous, anti-AVE resistance mechanisms. However such resistance mechanisms remain poorly investigated. In this study, we have characterized for the first time, a naturally-occurring preclinical @entity5 model (AY27) that exhibits intrinsic anti-AVE resistance despite treatment with @entity204 inducers like @entity2664 or @entity19486 -photodynamic therapy. Further mechanistic analysis revealed that this anti-AVE resistance was associated with a defect in exposing the important 'eat me' danger signal, surface- @entity4015 (ecto- @entity4015 / @entity4015 ). In an @entity204 setting, this defective ecto- @entity4015 further correlated with severely reduced phagocytic clearance of AY27 cells as well as the failure of these cells to activate AVE. Defective ecto- @entity4015 in response to @entity204 induction was a result of low endogenous @entity4015 protein levels (i.e. CRTlow-phenotype) in AY27 cells. Exogenous reconstitution of ecto-rCRT (recombinant- @entity4015 ) improved the phagocytic removal of @entity204 inducer-treated AY27 cells, and importantly, significantly increased their AVE-activating ability. Moreover, we found that a subset of @entity5 @entity1 of various @entity5 -types indeed possessed CALRlow or @entity5 . Remarkably, we found that tumoural CALRhigh-phenotype was predictive of positive clinical responses to therapy with @entity204 inducers (radiotherapy and @entity1311 ) in lung and @entity43 @entity1 , respectively. Furthermore, only in the @entity204 clinical setting, tumoural @entity4015 levels positively correlated with the levels of various phagocytosis-associated genes relevant for phagosome maturation or processing. Thus, we reveal the existence of a @entity5 cell-autonomous, anti-AVE or anti- @entity204 resistance mechanism that has profound clinical implications for anticancer immunotherapy and @entity5 predictive biomarker analysis.

Resistance to anticancer vaccination effect is controlled by a XXXX cell-autonomous phenotype that disrupts immunogenic phagocytic removal.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity43 :: ('MESH:D010051', 'Disease') :: ['ovarian cancer'] @entity5 :: ('MESH:D009369', 'Disease') :: ['CRTlow-tumours', 'cancer'] @entity2664 :: ('MESH:D008942', 'Chemical') :: ['mitoxantrone'] @entity1311 :: ('MESH:D017239', 'Chemical') :: ['paclitaxel'] @entity4015 :: ('811', 'Gene') :: ['CRT', 'CALR', 'calreticulin'] @entity204 :: ('MESH:D003643', 'Disease') :: ['ICD', 'Immunogenic cell death'] @entity19486 :: ('MESH:C004965', 'Chemical') :: ['hypericin']
@entity5 :: (MESH:D009369,Disease) :: ['cancer']
