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It is becoming evident that the therapeutic effect of reawakening the immune response is to limit tumor cell growth and expansion. The use of immune checkpoint inhibitors, like blocking antibodies against programmed cell death receptor (PD) 1 and/or cytotoxic T lymphocyte antigen (CTLA) 4 alone or in combination with other drugs, has led to unexpected positive results in some tumors but not all. Several other molecules inhibiting lymphocyte antitumor effector subsets have been discovered in the last 30 years. Herein, we focus on the leukocyte-associated immunoglobulin (Ig)-like receptor 1 (LAIR1/CD305). LAIR1 represents a typical immunoregulatory molecule expressed on almost all leukocytes, unlike other regulatory receptors expressed on discrete leukocyte subsets. It bears two immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in the intracytoplasmic protein domain involved in the downregulation of signals mediated by activating receptors. LAIR1 binds to several ligands, such as collagen I and III, complement component 1Q, surfactant protein D, adiponectin, and repetitive interspersed families of polypeptides expressed by erythrocytes infected with Plasmodium malariae. This would suggest LAIR1 involvement in several cell-to-cell interactions and possibly in metabolic regulation. The presence of both cellular and soluble forms of LAIR would indicate a fine regulation of the immunoregulatory activity, as happens for the soluble/exosome-associated forms of PD1 and CTLA4 molecules. As a consequence, LAIR1 appears to play a role in some autoimmune diseases and the immune response against tumor cells. The finding of LAIR1 expression on hematological malignancies, but also on some solid tumors, could open a rationale for the targeting of this molecule to treat neoplasia, either alone or in combination with other therapeutic options.

COVID-19 in immunocompromised patients is difficult to treat. SARS-CoV-2 interaction with the host immune system and the role of therapy still remains only partly understood. There are no data regarding the use of monoclonal antibodies and the combination of two antivirals in fighting viral replication and disease progression. We report the cases of two patients, both treated with rituximab for non-Hodgkin lymphoma and granulomatosis with polyangiitis, respectively, and both hospitalized for COVID-19 with positive SARS-CoV-2 RNAemia, who were successfully treated with a salvage combination therapy with sotrovimab, remdesivir and nirmatrelvir/ritonavir.

We prospectively studied immunological response against SARS-CoV-2 after vaccination among healthcare workers without (group A) and with previous infection (group B). The analyses were collected at T0 (before the BNT162b2), T1 (before the second dose), T2 and T6 (1 and 6 months after the second dose). For cellular immune response, the activation-induced cell marker assay was performed with CD4 and CD8 Spike peptide megapools expressed as Stimulation Index. For humoral immune response, we determined antibodies to Spike-1 and nucleocapsid protein. The linear mixed model compared specific times to T0. The CD4+ Spike response overall rate of change was significant at T1 (p = 0.038) and at T2 (p < 0.001), while decreasing at T6. For CD8+ Spike reactivity, the interaction between the time and group was significant (p = 0.0265), and the p value for group comparison was significant at the baseline (p = 0.0030) with higher SI in previously infected subjects. Overall, the anti-S Abs significantly increased from T1 to T6 compared to T0. The group B at T6 retained high anti-S titer (p < 0.001). At T6, in both groups we found a persistent humoral response and a high CD4+ T cell response able to cross recognize SARS-COV-2 variants including epsilon, even if not a circulating virus at that time.

Colorectal epithelium was the first long-term 3D organoid culture established in vitro. Identification of the key components essential for the long-term survival of the stem cell niche allowed an indefinite propagation of these cultures and the modulation of their differentiation into various lineages of mature intestinal epithelial cells. While these methods were eventually adapted to establish organoids from different organs, colorectal organoids remain a pioneering model for the development of new applications in health and disease. Several basic and applicative aspects of organoid culture, modeling, monitoring and testing are analyzed in this review. We also tackle the ethical problems of biobanking and distribution of these precious research tools, frequently confined in the laboratory of origin or condemned to destruction at the end of the project.

Quark–gluon plasma is an exotic state of matter that can emerge in heavy nuclei high-energy collisions. The ALICE collaboration reports the first observation of strangeness enhancement in proton–proton collisions, a possible signature of this state. At sufficiently high temperature and energy density, nuclear matter undergoes a transition to a phase in which quarks and gluons are not confined: the quark–gluon plasma (QGP) 1 . Such an exotic state of strongly interacting quantum chromodynamics matter is produced in the laboratory in heavy nuclei high-energy collisions, where an enhanced production of strange hadrons is observed 2 , 3 , 4 , 5 , 6 . Strangeness enhancement, originally proposed as a signature of QGP formation in nuclear collisions 7 , is more pronounced for multi-strange baryons. Several effects typical of heavy-ion phenomenology have been observed in high-multiplicity proton–proton (pp) collisions 8 , 9 , but the enhanced production of multi-strange particles has not been reported so far. Here we present the first observation of strangeness enhancement in high-multiplicity proton–proton collisions. We find that the integrated yields of strange and multi-strange particles, relative to pions, increases significantly with the event charged-particle multiplicity. The measurements are in remarkable agreement with the p–Pb collision results 10 , 11 , indicating that the phenomenon is related to the final system created in the collision. In high-multiplicity events strangeness production reaches values similar to those observed in Pb–Pb collisions, where a QGP is formed.

Deuterons are atomic nuclei composed of a neutron and a proton held together by the strong interaction. Unbound ensembles composed of a deuteron and a third nucleon have been investigated in the past using scattering experiments, and they constitute a fundamental reference in nuclear physics to constrain nuclear interactions and the properties of nuclei. In this work, K + − d and p − d femtoscopic correlations measured by the ALICE Collaboration in proton-proton ( p p ) collisions at s = 13     TeV at the Large Hadron Collider (LHC) are presented. It is demonstrated that correlations in momentum space between deuterons and kaons or protons allow us to study three-hadron systems at distances comparable with the proton radius. The analysis of the K + − d correlation shows that the relative distances at which deuterons and protons or kaons are produced are around 2 fm. The analysis of the p − d correlation shows that only a full three-body calculation that accounts for the internal structure of the deuteron can explain the data. In particular, the sensitivity of the observable to the short-range part of the interaction is demonstrated. These results indicate that correlations involving light nuclei in p p collisions at the LHC will also provide access to any three-body system in the strange and charm sectors.

The femtoscopic study of pairs of identical pions is particularly suited to investigate the effective source function of particle emission, due to the resulting Bose–Einstein correlation signal. In small collision systems at the LHC, pp in particular, the majority of the pions are produced in resonance decays, which significantly affect the profile and size of the source. In this work, we explicitly model this effect in order to extract the primordial source in pp collisions at s = 13  TeV from charged π – π correlations measured by ALICE. We demonstrate that the assumption of a Gaussian primordial source is compatible with the data and that the effective source, resulting from modifications due to resonances, is approximately exponential, as found in previous measurements at the LHC. The universality of hadron emission in pp collisions is further investigated by applying the same methodology to characterize the primordial source of K – p  pairs. The size of the primordial source is evaluated as a function of the transverse mass ( m T ) of the pairs, leading to the observation of a common scaling for both π – π and K – p  , suggesting a collective effect. Further, the present results are compatible with the m T scaling of the p – p  and p - Λ primordial source measured by ALICE in high multiplicity pp collisions, providing additional evidence for the presence of a common emission source for all hadrons in small collision systems at the LHC. This will allow the determination of the source function for any hadron–hadron pairs with high precision, granting access to the properties of the possible final-state interaction among pairs of less abundantly produced hadrons, such as strange or charmed particles.

A bstract A study of strange hadron production associated with hard scattering processes and with the underlying event is conducted to investigate the origin of the enhanced production of strange hadrons in small collision systems characterised by large charged-particle multiplicities. For this purpose, the production of the single-strange meson K S 0 and the double-strange baryon Ξ ± is measured, in each event, in the azimuthal direction of the highest- p T particle (“trigger” particle), related to hard scattering processes, and in the direction transverse to it in azimuth, associated with the underlying event, in pp collisions at s = 5.02 TeV and s = 13 TeV using the ALICE detector at the LHC. The per-trigger yields of K S 0 and Ξ ± are dominated by the transverse-to-leading production (i.e., in the direction transverse to the trigger particle), whose contribution relative to the toward-leading production is observed to increase with the event charged-particle multiplicity. The transverse-to-leading and the toward-leading Ξ ± / K S 0 yield ratios increase with the multiplicity of charged particles, suggesting that strangeness enhancement with multiplicity is associated with both hard scattering processes and the underlying event. The relative production of Ξ ± with respect to K S 0 is higher in transverse-to-leading processes over the whole multiplicity interval covered by the measurement. The K S 0 and Ξ ± per-trigger yields and yield ratios are compared with predictions of three different phenomenological models, namely P ythia 8.2 with the Monash tune, P ythia 8.2 with ropes and EPOS LHC. The comparison shows that none of them can quantitatively describe either the transverse-to-leading or the toward-leading yields of K S 0 and Ξ ± .