31 research outputs found
Serum Antibody Against NY-ESO-1 and XAGE1 Antigens Potentially Predicts Clinical Responses to Anti–Programmed Cell Death-1 Therapy in NSCLC
Introduction: Programmed cell death-1 (PD-1) inhibitors effectively treat NSCLC and prolong survival. Robust biomarkers for predicting clinical benefits of good response and long survival with anti-PD-1 therapy have yet to be identified; therefore, predictive biomarkers are needed to select patients with benefits.
Methods: We conducted a prospective study to explore whether serum antibody against NY-ESO-1 and/or XAGE1 cancer-testis antigens predicted primarily good clinical response and secondarily long survival with anti-PD-1 therapy for NSCLC. The serum antibody was detected by enzyme-linked immunosorbent assay, and tumor immune microenvironment and mutation burden were analyzed by immunohistochemistry and next-generation sequencing.
Results: In the discovery cohort (n = 13), six antibody-positive NSCLC cases responded to anti-PD-1 therapy (two complete and four partial responses), whereas seven antibody-negative NSCLC cases did not. Antibody positivity was associated with good response and survival, regardless of tumor programmed death ligand 1 (PD-L1) expression, mutation burden, and CD8+ T-cell infiltration. In the validation cohort (n = 75), 17 antibody-positive NSCLC cases responded well to anti-PD-1 therapy as compared with 58 negative NSCLC cases (objective response rate 65% versus 19%, p = 0.0006) and showed significantly prolonged progression-free survival and overall survival. Antibody titers highly correlated with tumor reduction rates. In the multivariate analysis, response biomarkers were tumor programmed death ligand 1 expression and antibody positivity, and only antibody positivity was a significantly better predictive biomarker of progression-free survival (hazard ratio = 0.4, p = 0.01) and overall survival (hazard ratio = 0.2, p = 0.004).
Conclusions: Our results suggest that NY-ESO-1 and/or XAGE1 serum antibodies are useful biomarkers for predicting clinical benefits in anti-PD-1 therapy for NSCLC and probably for other cancers
Three novel NY-ESO-1 epitopes bound to DRB1*0803, DQB1*0401 and DRB1*0901 recognized by CD4 T cells from CHP-NY-ESO-1-vaccinated patients
Three novel NY-ESO-1 CD4 T cell epitopes were identified using PBMC obtained from patients who were vaccinated with a complex of cholesterol-bearing hydrophobized pullulan (CHP) and NY-ESO-1 protein (CHP-NY-ESO-1). The restriction molecules were determined by antibody blocking and using various EBV-B cells with different HLA alleles as APC to present peptides to CD4 T cells. The minimal epitope peptides were determined using various N- and C-termini truncated peptides deduced from 18-mer overlapping peptides originally identified for recognition. Those epitopes were DRB1*0901-restricted NY-ESO-1 87-100. DQB1*0401-restricted NY-ESO-1 95-107 and DRB1*0803-restricted NY-ESO-1 124-134. CD4 T cells used to determine those epitope peptides recognized EBV-B cells or DC that were treated with recombinant NY-ESO-1 protein or NY-ESO-1-expressing tumor cell lysate, suggesting that the epitope peptides are naturally processed. These CD4 T cells showed a cytokine profile with Th1 characteristics. Furthermore, NY-ESO-1 87-100 peptide/HLA-DRB1*0901 tetramer staining was observed. Multiple Th1-type CD4 T cell responses are beneficial for inducing effective anti-tumor responses after NY-ESO-1 protein vaccination
Measurement of higher cumulants of net-charge multiplicity distributions in AuAu collisions at GeV
We report the measurement of cumulants () of the net-charge
distributions measured within pseudorapidity () in AuAu
collisions at GeV with the PHENIX experiment at the
Relativistic Heavy Ion Collider. The ratios of cumulants (e.g. ,
) of the net-charge distributions, which can be related to volume
independent susceptibility ratios, are studied as a function of centrality and
energy. These quantities are important to understand the quantum-chromodynamics
phase diagram and possible existence of a critical end point. The measured
values are very well described by expectation from negative binomial
distributions. We do not observe any nonmonotonic behavior in the ratios of the
cumulants as a function of collision energy. The measured values of and can be directly compared to lattice
quantum-chromodynamics calculations and thus allow extraction of both the
chemical freeze-out temperature and the baryon chemical potential at each
center-of-mass energy.Comment: 512 authors, 8 pages, 4 figures, 1 table. v2 is version accepted for
publication in Phys. Rev. C as a Rapid Communication. Plain text data tables
for the points plotted in figures for this and previous PHENIX publications
are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm
Transverse energy production and charged-particle multiplicity at midrapidity in various systems from to 200 GeV
Measurements of midrapidity charged particle multiplicity distributions,
, and midrapidity transverse-energy distributions,
, are presented for a variety of collision systems and energies.
Included are distributions for AuAu collisions at ,
130, 62.4, 39, 27, 19.6, 14.5, and 7.7 GeV, CuCu collisions at
and 62.4 GeV, CuAu collisions at
GeV, UU collisions at GeV,
Au collisions at GeV, HeAu collisions at
GeV, and collisions at
GeV. Centrality-dependent distributions at midrapidity are presented in terms
of the number of nucleon participants, , and the number of
constituent quark participants, . For all collisions
down to GeV, it is observed that the midrapidity data
are better described by scaling with than scaling with . Also presented are estimates of the Bjorken energy density,
, and the ratio of to ,
the latter of which is seen to be constant as a function of centrality for all
systems.Comment: 706 authors, 32 pages, 20 figures, 34 tables, 2004, 2005, 2008, 2010,
2011, and 2012 data. v2 is version accepted for publication in Phys. Rev.
Measurement of jet-medium interactions via direct photon-hadron correlations in AuAu and Au collisions at GeV
We present direct photon-hadron correlations in 200 GeV/A AuAu, Au
and collisions, for direct photon from 5--12 GeV/, collected
by the PHENIX Collaboration in the years from 2006 to 2011. We observe no
significant modification of jet fragmentation in Au collisions,
indicating that cold nuclear matter effects are small or absent. Hadrons
carrying a large fraction of the quark's momentum are suppressed in AuAu
compared to and Au. As the momentum fraction decreases, the
yield of hadrons in AuAu increases to an excess over the yield in
collisions. The excess is at large angles and at low hadron and is most
pronounced for hadrons associated with lower momentum direct photons.
Comparison to theoretical calculations suggests that the hadron excess arises
from medium response to energy deposited by jets.Comment: 578 authors from 80 institutions, 11 pages, 7 figures, data from
2007, 2008, 2010, and 2011. v2 is version accepted for publication in
Physical Review C. Plain text data tables for the points plotted in figures
for this and previous PHENIX publications are (or will be) publicly available
at http://www.phenix.bnl.gov/papers.htm
Turicibacter and Acidaminococcus predict immune-related adverse events and efficacy of immune checkpoint inhibitor
IntroductionImmune checkpoint inhibitors have had a major impact on cancer treatment. Gut microbiota plays a major role in the cancer microenvironment, affecting treatment response. The gut microbiota is highly individual, and varies with factors, such as age and race. Gut microbiota composition in Japanese cancer patients and the efficacy of immunotherapy remain unknown. MethodsWe investigated the gut microbiota of 26 patients with solid tumors prior to immune checkpoint inhibitor monotherapy to identify bacteria involved in the efficacy of these drugs and immune-related adverse events (irAEs).ResultsThe genera Prevotella and Parabacteroides were relatively common in the group showing efficacy towards the anti-PD-1 antibody treatment (effective group). The proportions of Catenibacterium (P = 0.022) and Turicibacter (P = 0.049) were significantly higher in the effective group than in the ineffective group. In addition, the proportion of Desulfovibrion (P = 0.033) was significantly higher in the ineffective group. Next, they were divided into irAE and non-irAE groups. The proportions of Turicibacter (P = 0.001) and Acidaminococcus (P = 0.001) were significantly higher in the group with irAEs than in those without, while the proportions of Blautia (P = 0.013) and the unclassified Clostridiales (P = 0.027) were significantly higher in the group without irAEs than those with. Furthermore, within the Effective group, Acidaminococcus and Turicibacter (both P = 0.001) were more abundant in the subgroup with irAEs than in those without them. In contrast, Blautia (P = 0.021) and Bilophila (P= 0.033) were statistically significantly more common in those without irAEs.DiscussionOur Study suggests that the analysis of the gut microbiota may provide future predictive markers for the efficacy of cancer immunotherapy or the selection of candidates for fecal transplantation for cancer immunotherapy