264 research outputs found
Prognostic value of B cells in cutaneous melanoma
Background: Measures of the adaptive immune response have prognostic and predictive associations in melanoma and other cancer types. Specifically, intratumoral T cell density and function have considerable prognostic and predictive value in skin cutaneous melanoma (SKCM). Less is known about the significance of tumor-infiltrating B cells in SKCM. Our goal was to understand the prognostic and predictive value of B cell phenotypic subsets in SKCM using RNA sequencing. Methods: We used our previously published algorithm, V'DJer, to assemble B cell receptor (BCR) repertoires and estimate diversity from short-read RNA sequencing (RNA-seq). We applied machine learning-based cellular phenotype classifiers to measure relative similarity of bulk tumor sample gene expression profiles and different B cell phenotypes. We assessed these aspects of B cell biology in 473 SKCM from the Cancer Genome Atlas Project (TCGA) as well as in RNA-seq data corresponding to tumor samples procured from patients who received CTLA-4 and PD-1 inhibitors for metastatic SKCM. Results: We found that the BCR repertoire was associated with different clinical factors, such as tumor tissue site and sex. However, increased clonality of the BCR repertoire was favorably prognostic in SKCM and was prognostic even after first conditioning on various clinical factors. Mutation burden was not correlated with any BCR measurement, and no specific mutation had an altered BCR repertoire. Lack of an assembled BCR in pre-treatment tumor tissues was associated with a lack of anti-tumor response to a CTLA-4 inhibitor in metastatic SKCM. Conclusions: These findings suggest an important prognostic and predictive role for B cell characteristics in SKCM. This has implications for melanoma immunobiology and potential development of immunogenomics features to predict survival and response to immunotherapy
Machine-learning prediction of tumor antigen immunogenicity in the selection of therapeutic epitopes
Current tumor neoantigen calling algorithms primarily rely on epitope/major histocompatibility complex (MHC) binding affinity predictions to rank and select for potential epitope targets. These algorithms do not predict for epitope immunogenicity using approaches modeled from tumor-specific antigen data. Here, we describe peptide-intrinsic biochemical features associated with neoantigen and minor histocompatibility mismatch antigen immunogenicity and present a gradient boosting algorithm for predicting tumor antigen immunogenicity. This algorithm was validated in two murine tumor models and demonstrated the capacity to select for therapeutically active antigens. Immune correlates of neoantigen immunogenicity were studied in a pan-cancer data set from The Cancer Genome Atlas and demonstrated an association between expression of immunogenic neoantigens and immunity in colon and lung adenocarcinomas. Lastly, we present evidence for expression of an out-of-frame neoantigen that was capable of driving antitumor cytotoxic T-cell responses. With the growing clinical importance of tumor vaccine therapies, our approach may allow for better selection of therapeutically relevant tumor-specific antigens, including nonclas-sic out-of-frame antigens capable of driving antitumor immunity
HOPX functions as a tumour suppressor in head and neck cancer.
Head and neck squamous cell carcinoma (HNSCC) is generalized term that encompasses a diverse group of cancers that includes tumours of the oral cavity (OSCC), oropharynx (OPSCC) and nasopharynx (NPC). Genetic alterations that are common to all HNSCC types are likely to be important for squamous carcinogenesis. In this study, we have investigated the role of the homeodomain-only homeobox gene, HOPX, in the pathogenesis of HNSCC. We show that HOPX mRNA levels are reduced in OSCC and NPC cell lines and tissues and there is a general reduction of HOPX protein expression in these tumours and OPSCCs. HOPX promoter methylation was observed in a subset of HNSCCs and was associated with a worse overall survival in HPV negative tumours. RNAseq analysis of OSCC cells transfected with HOPX revealed a widespread deregulation of the transcription of genes related to epithelial homeostasis and ectopic over-expression of HOPX in OSCC and NPC cells inhibited cell proliferation, plating efficiency and migration, and enhanced sensitivity to UVA-induced apoptosis. Our results demonstrate that HOPX functions as a tumour suppressor in HNSCC and suggest a central role for HOPX in suppressing epithelial carcinogenesis
Heavy Quarks and Heavy Quarkonia as Tests of Thermalization
We present here a brief summary of new results on heavy quarks and heavy
quarkonia from the PHENIX experiment as presented at the "Quark Gluon Plasma
Thermalization" Workshop in Vienna, Austria in August 2005, directly following
the International Quark Matter Conference in Hungary.Comment: 8 pages, 5 figures, Quark Gluon Plasma Thermalization Workshop
(Vienna August 2005) Proceeding
Single Electrons from Heavy Flavor Decays in p+p Collisions at sqrt(s) = 200 GeV
The invariant differential cross section for inclusive electron production in
p+p collisions at sqrt(s) = 200 GeV has been measured by the PHENIX experiment
at the Relativistic Heavy Ion Collider over the transverse momentum range $0.4
<= p_T <= 5.0 GeV/c at midrapidity (eta <= 0.35). The contribution to the
inclusive electron spectrum from semileptonic decays of hadrons carrying heavy
flavor, i.e. charm quarks or, at high p_T, bottom quarks, is determined via
three independent methods. The resulting electron spectrum from heavy flavor
decays is compared to recent leading and next-to-leading order perturbative QCD
calculations. The total cross section of charm quark-antiquark pair production
is determined as sigma_(c c^bar) = 0.92 +/- 0.15 (stat.) +- 0.54 (sys.) mb.Comment: 329 authors, 6 pages text, 3 figures. Submitted to Phys. Rev. Lett.
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
Nuclear Modification of Electron Spectra and Implications for Heavy Quark Energy Loss in Au+Au Collisions at sqrt(s_NN)=200 GeV
The PHENIX experiment has measured mid-rapidity transverse momentum spectra
(0.4 < p_T < 5.0 GeV/c) of electrons as a function of centrality in Au+Au
collisions at sqrt(s_NN)=200 GeV. Contributions from photon conversions and
from light hadron decays, mainly Dalitz decays of pi^0 and eta mesons, were
removed. The resulting non-photonic electron spectra are primarily due to the
semi-leptonic decays of hadrons carrying heavy quarks. Nuclear modification
factors were determined by comparison to non-photonic electrons in p+p
collisions. A significant suppression of electrons at high p_T is observed in
central Au+Au collisions, indicating substantial energy loss of heavy quarks.Comment: 330 authors, 6 pages text, 3 figures. Submitted to Phys. Rev. Lett.
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
Measurement of Transverse Single-Spin Asymmetries for Mid-rapidity Production of Neutral Pions and Charged Hadrons in Polarized p+p Collisions at sqrt(s) = 200 GeV
The transverse single-spin asymmetries of neutral pions and non-identified
charged hadrons have been measured at mid-rapidity in polarized proton-proton
collisions at sqrt(s) = 200 GeV. The data cover a transverse momentum (p_T)
range 0.5-5.0 GeV/c for charged hadrons and 1.0-5.0 GeV/c for neutral pions, at
a Feynman-x (x_F) value of approximately zero. The asymmetries seen in this
previously unexplored kinematic region are consistent with zero within
statistical errors of a few percent. In addition, the inclusive charged hadron
cross section at mid-rapidity from 0.5 < p_T < 7.0 GeV/c is presented and
compared to NLO pQCD calculations. Successful description of the unpolarized
cross section above ~2 GeV/c using NLO pQCD suggests that pQCD is applicable in
the interpretation of the asymmetry results in the relevant kinematic range.Comment: 331 authors, 6 pages text, 2 figures, 3 tables. Submitted to Phys.
Rev. Lett. 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
Formation of dense partonic matter in relativistic nucleus-nucleus collisions at RHIC: Experimental evaluation by the PHENIX collaboration
Extensive experimental data from high-energy nucleus-nucleus collisions were
recorded using the PHENIX detector at the Relativistic Heavy Ion Collider
(RHIC). The comprehensive set of measurements from the first three years of
RHIC operation includes charged particle multiplicities, transverse energy,
yield ratios and spectra of identified hadrons in a wide range of transverse
momenta (p_T), elliptic flow, two-particle correlations, non-statistical
fluctuations, and suppression of particle production at high p_T. The results
are examined with an emphasis on implications for the formation of a new state
of dense matter. We find that the state of matter created at RHIC cannot be
described in terms of ordinary color neutral hadrons.Comment: 510 authors, 127 pages text, 56 figures, 1 tables, LaTeX. Submitted
to Nuclear Physics A as a regular article; v3 has minor changes in response
to referee comments. 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
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