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Studies of the immune landscape led to breakthrough trials of programmed death-1 (PD-1) inhibitors for recurrent/metastatic head and neck squamous cell carcinoma therapy. This study investigated the timing, influence of somatic copy-number alterations (SCNAs), and clinical implications of PD-L1 and immune-cell patterns in oral precancer (OPC).The authors evaluated spatial CD3, CD3/8, and CD68 density (cells/mmEpithelial, but not CD68 immune-cell, PD-L1 expression was detected in 28% of OPCs, correlated with immune-cell infiltration, 9p21.3 loss of heterozygosity (LOH), and inferior oral cancer-free survival (OCFS), notably in OPCs with low CD3/8 cell density, dysplasia, and/or 9p21.3 LOH. High CD3/8 cell density in dysplastic lesions predicted better OCFS and eliminated the excess risk associated with prior oral cancer and dysplasia. PD-L1 and CD3/8 patterns revealed inferior OCFS in PD-L1 high intrinsic induction and dysplastic immune-cold subgroups.This report provides spatial insight into the immune landscape and drivers of OPCs, and a publicly available immunogenomic data set for future precancer interrogation. The data suggest that 9p21.3 LOH triggers an immune-hot inflammatory phenotype; whereas increased 9p deletion size encompassing CD274 at 9p24.1 may contribute to CD3/8 and PD-L1 depletion during invasive transition. The inferior OCFS in PD-L1-high, immune-cold OPCs support the development of T-cell recruitment strategies.

da Costa Souza P, Parra E R, Atanazio M J, da Silva O B, Noleto G S, Ab’Saber A M, de Morais Fernezlian S, Takagaki T & Capelozzi V L (2012) Histopathology 61, 587–596 Different morphology, stage and treatment affect immune cell infiltration and long-term outcome in patients with non-small-cell lung carcinoma Aims: Development of effective immune-based therapies for patients with non-small-cell lung carcinoma (NSCLC) depends on an accurate characterization of complex interactions that occur between immune cells and the tumour environment. Methods and results: Innate and adaptive immune responses were evaluated in relation to prognosis in 65 patients with surgically excised NSCLC. Immunohistochemistry and morphometry were used to determine the abundance and distribution of immune cells. We found low numbers of immune cells and levels of cytokines in the tumour environment when compared with surrounding parenchyma. Smoking was associated inversely with the adaptive immune response and directly with innate immunity. We observed a prominent adaptive immune response in squamous cell carcinomas (SCC) but greater innate immune responses in adenocarcinomas and large cell carcinomas. Cox model analysis showed a low risk of death for smoking 16.81% and macrophages/monocytes >4.5%. Collectively, the data indicate that in NSCLC there is not a substantive local immune cell infiltrate within the tumour. Conclusion: Although immune cell infiltration is limited in NSCLC it appears to have an impact on prognosis and this may be of relevance for new immunotherapeutic approaches.

Aims: To compare septal and vascular matrix remodelling, vascular occlusion, pulmonary function tests and survival between two groups: one with idiopathic non-specific interstitial pneumonia (NSIP) and one with NSIP associated with systemic sclerosis (SSc). Methods and results: Pulmonary biopsy specimens were examined from 40 patients, 22 with NSIP and 18 with NSIP associated with SSc. The content of septal collagen and elastic fibres, as well as the elastic fibres in the vascular interstitium, were higher in the SSc group (P = 0.01, P = 0.001 and P

Aims: Organizing pneumonia (OP) is an inflammatory lung disease characterized histologically by intraluminal plugs involving alveolar ducts and alveoli. The aim was to examine extracellular matrix repair and remodelling in 12 cases of idiopathic OP and compare these with 11 cases of secondary OP. Methods and results: Collagen/elastic fibre density, myofibroblast proliferation, microvascular density and endothelial activity in the intraluminal plugs were evaluated by histochemistry, immunohistochemistry and morphometry. The density of the collagen system fibres was greater in plugs of idiopathic OP when compared with secondary OP (P

Aims : Structural remodelling in acute and chronic idiopathic interstitial pneumonia (IIP) has been extensively investigated, but little attention has been directed to the elastic tissue in these situations. The aim of this study was to determine whether elastic deposition accompanies collagen deposition in the four major histological patterns of IIP: diffuse alveolar damage (DAD), organizing pneumonia (OP), non-specific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP). Methods and results : We measured, by image analysis, the content of fibres of the collagenous and elastic systems of the alveolar septum in histological slides of open lung biopsies, using the picrosirius-polarization method and Weigert's resorcin–fuchsin stain, respectively. Five groups were studied: 10 cases of DAD; nine cases of OP; nine cases of NSIP; and 10 cases of UIP. Four normal lungs were used for comparison. The content of collagen fibres was significantly higher in UIP when compared to DAD, NSIP, OP and normal lung. The content of elastic fibres was increased in comparison with normal lungs but this was not significantly different among the histological patterns. Conclusion : Acute and chronic IIP cause a similar increase in the collagen and elastic contents of the lungs, representing a process of ‘fibroelastosis’ rather than an exclusive process of fibrosis. A profibrogenic mechanism is responsible for the unparallelled collagen augmentation observed in UIP subjects, the nature of which is yet to be determined.