Recent advances in cancer immunotherapy have clearly shown that checkpoint-based immunotherapy is effective in a small subgroup of cancer patients. However, no effective predictive biomarker has been ...identified so far. The major histocompatibility complex, better known in humans as human leukocyte antigen (HLA), is a very polymorphic gene complex consisting of more than 200 genes. It has a crucial role in activating an appropriate host immune response against pathogens and tumor cells by discriminating self and non-self peptides. Several lines of evidence have shown that down-regulation of expression of HLA class I antigen derived peptide complexes by cancer cells is a mechanism of tumor immune escape and is often associated to poor prognosis in cancer patients. In addition, it has also been shown that HLA class I and II antigen expression, as well as defects in the antigen processing machinery complex, may predict tumor responses in cancer immunotherapy. Nevertheless, the role of HLA in predicting tumor responses to checkpoint-based immunotherapy is still debated. In this review, firstly, we will describe the structure and function of the HLA system. Secondly, we will summarize the HLA defects and their clinical significance in cancer patients. Thirdly, we will review the potential role of the HLA as a predictive biomarker for checkpoint-based immunotherapy in cancer patients. Lastly, we will discuss the potential strategies that may restore HLA function to implement novel therapeutic strategies in cancer patients.
The strong intervening absorption system at redshift 1.15 towards the very bright quasar HE 0515−4414 is the most studied absorber for measuring possible cosmological variations in the fine-structure ...constant,
α
. We observed HE 0515−4414 for 16.1 h with the Very Large Telescope and present here the first constraint on relative variations in
α
with parts-per-million (ppm) precision from the new ESPRESSO spectrograph: Δ
α
/
α
= 1.3 ± 1.3
stat
± 0.4
sys
ppm. The statistical uncertainty (1
σ
) is similar to the ensemble precision of previous large samples of absorbers and derives from the high signal-to-noise ratio achieved (≈105 per 0.4 km s
−1
pixel). ESPRESSO’s design, and the calibration of our observations with its laser frequency comb, effectively removed wavelength calibration errors from our measurement. The high resolving power of our ESPRESSO spectrum (
R
= 145 000) enabled the identification of very narrow components within the absorption profile, allowing a more robust analysis of Δ
α
/
α
. The evidence for the narrow components is corroborated by their correspondence with previously detected molecular hydrogen and neutral carbon. The main remaining systematic errors arise from ambiguities in the absorption profile modelling, effects from redispersing the individual quasar exposures, and convergence of the parameter estimation algorithm. All analyses of the spectrum, including systematic error estimates, were initially blinded to avoid human biases. We make our reduced ESPRESSO spectrum of HE 0515−4414 publicly available for further analysis. Combining our ESPRESSO result with 28 measurements, from other spectrographs, in which wavelength calibration errors have been mitigated yields a weighted mean Δ
α
/
α
= −0.5 ± 0.5
stat
± 0.4
sys
ppm at redshifts 0.6−2.4.
Abstract
We present high-precision radial velocities (RVs) from the HARPS-N spectrograph for HD 79210 and HD 79211, two M0V members of a gravitationally bound binary system. We detect a planet ...candidate with a period of
24.421
−
0.017
+
0.016
days around HD 79211 in these HARPS-N RVs, validating the planet candidate originally identified in CARMENES RV data alone. Using HARPS-N, CARMENES, and RVs spanning a total of 25 yr, we further refine the planet candidate parameters to
P
= 24.422 ± 0.014 days,
K
= 3.19 ± 0.27 m s
−1
,
M
sin
i
= 10.6 ± 1.2
M
⊕
, and
a
= 0.142 ± 0.005 au. We do not find any additional planet candidate signals in the data of HD 79211, nor do we find any planet candidate signals in HD 79210. This system adds to the number of exoplanets detected in binaries with M-dwarf members and serves as a case study for planet formation in stellar binaries.
ABSTRACT
M-dwarfs are the most abundant stars in the galaxy and popular targets for exoplanet searches. However, their intrinsic faintness and complex spectra inhibit precise characterization. We ...only know of dozens of M-dwarfs with fundamental parameters of mass, radius, and effective temperature characterized to better than a few per cent. Eclipsing binaries remain the most robust means of stellar characterization. Here we present two targets from the Eclipsing Binary Low Mass (EBLM) survey that were observed with K2: EBLM J0055-00 and EBLM J2217-04. Combined with HARPS and CORALIE spectroscopy, we measure M-dwarf masses with precisions better than 5 per cent, radii better than 3 per cent, and effective temperatures on order 1 per cent. However, our fits require invoking a model to derive parameters for the primary star and fitting the M-dwarf using the transit and radial velocity observations. By investigating three popular stellar models, we determine that the model uncertainty in the primary star is of similar magnitude to the statistical uncertainty in the model fits of the secondary M-dwarf. Therefore, whilst these can be considered benchmark M-dwarfs, we caution the community to consider model uncertainty when pushing the limits of precise stellar characterization.
Observations of metal absorption systems in the spectra of distant quasars allow one to constrain a possible variation of the fine-structure constant throughout the history of the Universe. Such a ...test poses utmost demands on the wavelength accuracy and previous studies were limited by systematics in the spectrograph wavelength calibration. A substantial advance in the field is therefore expected from the new ultra-stable high-resolution spectrograph E
SPRESSO
, which was recently installed at the VLT. In preparation of the fundamental physics related part of the E
SPRESSO
GTO program, we present a thorough assessment of the E
SPRESSO
wavelength accuracy and identify possible systematics at each of the different steps involved in the wavelength calibration process. Most importantly, we compare the default wavelength solution, which is based on the combination of Thorium-Argon arc lamp spectra and a Fabry-Pérot interferometer, to the fully independent calibration obtained from a laser frequency comb. We find wavelength-dependent discrepancies of up to 24 m s
−1
. This substantially exceeds the photon noise and highlights the presence of different sources of systematics, which we characterize in detail as part of this study. Nevertheless, our study demonstrates the outstanding accuracy of E
SPRESSO
with respect to previously used spectrographs and we show that constraints of a relative change of the fine-structure constant at the 10
−6
level can be obtained with E
SPRESSO
without being limited by wavelength calibration systematics.
Raman scattering enables unforeseen uses for the laser guide-star system of the Very Large Telescope. Here, we present the observation of one up-link sodium laser beam acquired with the ESPRESSO ...spectrograph at a resolution λ/Δλ∼140 000. In 900 s on source, we detect the pure rotational Raman lines of ^{16}O_{2}, ^{14}N_{2}, and ^{14}N^{15}N (tentatively) up to rotational quantum numbers J of 27, 24, and 9, respectively. We detect the ^{16}O_{2} fine-structure lines induced by the interaction of the electronic spin S and end-over-end rotational angular momentum N in the electronic ground state of this molecule up to N=9. The same spectrum also reveals the ν_{1←0} rotational-vibrational Q-branch for ^{16}O_{2} and ^{14}N_{2}. These observations demonstrate the potential of using laser guide-star systems as accurate calibration sources for characterizing new astronomical spectrographs.
ABSTRACT
We present confirmation of the planetary nature of PH-2b, as well as the first mass estimates for the two planets in the Kepler-103 system. PH-2b and Kepler-103c are both long-period and ...transiting, a sparsely populated category of exoplanets. We use Kepler light-curve data to estimate a radius, and then use HARPS-N radial velocities to determine the semi-amplitude of the stellar reflex motion and, hence, the planet mass. For PH-2b we recover a 3.5σ mass estimate of $M_\mathrm{ p} = 109^{+30}_{-32}$ M⊕ and a radius of Rp = 9.49 ± 0.16 R⊕. This means that PH-2b has a Saturn-like bulk density and is the only planet of this type with an orbital period P > 200 d that orbits a single star. We find that Kepler-103b has a mass of $M_{\text{p,b}} = 11.7^{+4.31}_{-4.72}$ M⊕ and Kepler-103c has a mass of $M_{\text{p,c}} = 58.5^{+11.2}_{-11.4}$ M⊕. These are 2.5σ and 5σ results, respectively. With radii of $R_{\text{p,b}} = 3.49^{+0.06}_{-0.05}$ R⊕ and $R_{\text{p,c}} = 5.45^{+0.18}_{-0.17}$ R⊕, these results suggest that Kepler-103b has a Neptune-like density, while Kepler-103c is one of the highest density planets with a period P > 100 d. By providing high-precision estimates for the masses of the long-period, intermediate-mass planets PH-2b and Kepler-103c, we increase the sample of long-period planets with known masses and radii, which will improve our understanding of the mass–radius relation across the full range of exoplanet masses and radii.
Exoplanets can evolve significantly between birth and maturity, as their atmospheres, orbits, and structures are shaped by their environment. Young planets (<1 Gyr) offer an opportunity to probe the ...critical early stages of this evolution, where planets evolve the fastest. However, most of the known young planets orbit prohibitively faint stars. We present the discovery of two planets transiting HD 63433 (TOI 1726, TIC 130181866), a young Sun-like ( ) star. Through kinematics, lithium abundance, and rotation, we confirm that HD 63433 is a member of the Ursa Major moving group (τ = 414 23 Myr). Based on the TESS light curve and updated stellar parameters, we estimate that the planet radii are 2.15 0.10 R⊕ and 2.67 0.12 R⊕, the orbital periods are 7.11 and 20.55 days, and the orbital eccentricities are lower than about 0.2. Using High Accuracy Radial velocity Planet Searcher for the Northern hemisphere velocities, we measure the Rossiter-McLaughlin signal of the inner planet, demonstrating that the orbit is prograde. Since the host star is bright (V = 6.9), both planets are amenable to transmission spectroscopy, radial velocity measurements of their masses, and more precise determination of the stellar obliquity. This system is therefore poised to play an important role in our understanding of planetary system evolution in the first billion years after formation.
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