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The inhibitory molecule CD85/LIR-1/ILT2 has been detected previously on the surface of a small proportion of T lymphocytes. In this study, evidence is provided that, although only a fraction of CD3+ cells are stained by mAb specific for CD85/LIR-1/ILT2 on their surface, this inhibitory receptor is present in the cytoplasm of all T lymphocytes, and that it is detectable on the surface of all T cell clones by the M402 mAb. Biochemical analyses further demonstrate that CD85/LIR-1/ILT2 is present in all T clones analyzed, and that the protein is tyrosine-phosphorylated. Expression of mRNA coding for CD85/LIR-1/ILT2 has been assessed by RT-PCR. Notably, in the NKL cell line and in one T cell clone, amplification of the messenger required 30 cycles only, whereas, in other T cell clones, an amplification product was detected by increasing the number of cycles. CD85/LIR-1/ILT2 inhibits CD3/TCR-mediated activation in both CD4+ and CD8+ clones, and it down-regulates Ag recognition by CD8+ cells in a clonally distributed fashion. Addition of anti-ILT2 HP-F1 mAb in the cytolytic assay enhances target cell lysis mediated by Ag-specific CTL. This could be due to interference of the mAb with receptor/ligand interactions. In contrast, HP-F1 mAb cross-linking triggers inhibitory signals that reduce cytotoxicity. CD85/LIR-1/ILT2 also controls responses to recall Ags and, in low responders, its engagement sharply increases T cell proliferation. The inhibitory function of the molecule is also confirmed by its ability to reduce CD3/TCR-induced intracellular Ca2+ mobilization.

Ac cu mu la ti ng evi den ce shows that chro nic in fl am ma tion is as so cia ted to in crea sed ri sk of can cer. An in fl am ma to ry com po ne nt is pre se nt al so in the mic roen vi ron me nt of tu mou rs epi de mio lo gi cal ly un re la ted to in fl am ma tion. Exten si ve in ves ti ga tio ns over the pa st de ca de ha ve un co ve red ma ny of the im por ta nt mec ha nis tic pat hways un der lyi ng can ce r-re la ted in fl am ma tion. Pat hways lin ki ng in fl am ma tion and can cer ha ve been iden ti fi ed: an in trin sic one (dri ven by ge ne tic even ts that cau se neop la sia) and an extrin sic one (dri ven by in fl am ma to ry con di tio ns whi ch pre dis po se to can cer). Smoul de ri ng in fl am ma tion is a com po ne nt of the tu mour mic roen vi ron me nt and is a re cog ni zed hal lma rk of can cer. Key or ches tra to rs at the in tersec tion of the in trin sic and extrin sic pat hways in clu de tran scrip tion fac to rs (e.g. Nuc lear Fac tor kap pa-B, NFκB) that mo du la te the in fl am ma to ry res pon se throu gh so lub le me dia to rs (cyto ki nes, che mo ki nes) and cel lu lar com po nen ts (e.g. tu mo r-as so cia ted mac rop ha ges), pro mo ti ng tu mo ri gene sis. NFκB aids in the pro li fe ra tion and sur vi val of ma lig na nt cel ls, pro mo tes an gio ge ne sis and me tas ta sis, sub ver ts adap ti ve im mu ni ty, and al te rs res pon ses to hor mo nes and che mot he ra peu tic agen ts. Emer gi ng evi den ce al so sug ges ts that per sis te nt in fl am ma tion pro mo tes ge ne tic in sta bi li ty. Thus, can ce r-re la ted in fl am ma tion rep re sen ts a tar get for in no va ti ve diag nos tic and the ra peu tic stra te gies. Key wor ds: can ce r-re la ted in fl am ma tion; cyto ki nes; che mo ki nes; mac rop ha ges Re cei ved: July 29, 2011 Ac cep ted: Septem ber 19, 2011 Mo le cu lar pat hways in can ce r-re la ted in fl am ma tion In tro duc tionThe Ger man Pat ho lo gi st Vir chow is cre di ted wi th sug ges ti ng the ca sual li nk be tween in fl am ma tion and can cer in the 19 th cen tu ry (1). This con clu sion was ba sed on the ob ser va tion that tu mou rs of ten de ve lo ped in the set ti ng of chro nic in fl am ma tion and that in fl am ma to ry cel ls we re pre se nt in tumour biop sy spe ci me ns. Epi de mio lo gi cal stu dies ha ve re vea led that chro nic in fl am ma tion pre dis poses to diff e re nt types of can cer. It is es ti ma ted that un der lyi ng in fec tio ns and in fl am ma to ry res pon ses are lin ked to 15-20% of all dea th from can cer worldwi de (2,3). The trig ge rs of chro nic in fl am ma tion whi ch in crea se can cer ri sk in clu de mic ro bial in fectio ns (e.g. He li co bac ter pylo ri for gas tric can cer and mu co sal lympho ma), au toim mu ne di sea ses (e.g. in fl am ma to ry bowel di sea se for co lon can cer), and crypto ge nic in fl am ma to ry con di tio ns of un cer tain ori gin (e.g. pros ta ti tis for pros ta te can cer). The stron ge st evi den ce in hu ma ns of the ro le of infl am ma tion in can cer has been pro vi ded by s...

Background Surgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction. Methods This international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index <20), moderate lockdowns (20–60), and full lockdowns (>60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov , NCT04384926 . Findings Of eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16–30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77–0·84; p<0·0001), and full lockdowns with a 15·0% rate (1775 of 11 827; HR 0·51, 0·50–0·53; p<0·0001). In sensitivity analyses, including adjustment for SARS-CoV-2 case notification rates, moderate lockdowns (HR 0·84, 95% CI 0·80–0·88; p<0·001), and full lockdowns (0·57, 0·54–0·60; p<0·001), remained independently associated with non-operation. Surgery beyond 12 weeks from diagnosis in patients without neoadjuvant therapy increased during lockdowns (374 [9·1%] of 4521 in light restrictions, 317 [10·4%] of 3646 in moderate lockdowns, 2001 [23·8%] of 11 827 in full lockdowns), although there were no differences in resectability rates observed with longer delays. Interpretation Cancer surgery systems worldwide were fragile to lockdowns, with one in seven patients who were in regions with full lockdowns not undergoing planned surgery and experiencing longer preoperative delays. Although short-term oncological outcomes were not compromised in those selected for surgery, delays and non-operations might lead to long-term reductions in survival. During current and future periods of societal restriction, the resilience of elective surgery systems requires strengthening, which might include...

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The claustrum is a thin layer of gray matter that is at the center of an active scientific debate. Recently, Constrained Spherical Deconvolution (CSD) tractography has proved to be an extraordinary tool allowing to track white matter fibers from cortex to cortical and subcortical targets with subvoxel resolution. The aim of this study was to evaluate claustral connectivity in the human brain. Ten normal brains were analyzed by using the High Angular Resolution Diffusion Imaging CSD-based technique. Tractography revealed 4 groups of white matter fibers connecting the claustrum with the brain cortex: Anterior, posterior, superior, and lateral. The anterior and posterior cortico-claustral tracts connected the claustrum to prefrontal cortex and visual areas. The superior tract linked the claustrum with sensory-motor areas, while the lateral pathway connected the claustrum to the auditory cortex. In addition, we demonstrated a claustral medial pathway connecting the claustrum with the basal ganglia, specifically with caudate nucleus, putamen, and globus pallidus. An interesting and exciting new finding was the demonstration of a bilateral connection between claustrum and contralateral cortical areas and a well-represented interclaustral communication with interconnection bundles interspersed within the bulk of the trunk of the corpus callosum. The physiological and pathophysiological relevance of these findings are discussed.

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