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Simple Summary: TIL scoring has been recommended as a biomarker in routine clinical practice in breast cancer patients. Currently, the standard of care for early breast cancer is neoadjuvant treatment. Recent studies have demonstrated the additional predictive value of TIL scoring to the residual cancer burden after neoadjuvant treatment. Although guidelines have been published, the reliability of this biomarker in treated tumor samples has not yet been evaluated. Here, we show that there is good inter-pathologist reproducibility for TIL scoring in patients with clear residual tumor tissue. However, in patients with a (near-)complete response, there is not. This is significant because this demonstrates that it could be a reliable biomarker and help guide adjuvant treatment decisions. Neoadjuvant chemotherapy (NAC) is now the standard of care for patients with locally advanced breast cancer (BC). TIL scoring is prognostic and adds predictive value to the residual cancer burden evaluation after NAC. However, NAC induces changes in the tumor, and the reliability of TIL scoring in post-NAC samples has not yet been studied. H&E- and dual CD3/CD20 chromogenic IHC-stained tissues were scored for stromal and intra-tumoral TIL by two experienced pathologists on pre- and post-treatment BC tissues. Digital TIL scoring was performed using the HALO® image analysis software (version 2.2). In patients with residual disease, we show a good inter-pathologist correlation for stromal TIL on H&E-stained tissues (CCC value 0.73). A good correlation for scoring with both staining methods (CCC 0.81) and the digital TIL scoring (CCC 0.77) was also observed. Overall concordance for TIL scoring in patients with a complete response was however poor. This study reveals there is good reliability for TIL scoring in patients with detectable residual tumors after NAC treatment, which is comparable to the scoring of untreated breast cancer patients. Based on the good consistency observed with digital TIL scoring, the development of a validated algorithm in the future might be advantageous. [ABSTRACT FROM AUTHOR]

Simple Summary: The development of new treatments for patients with neuroendocrine neoplasms (NENs) is imperative. Immunotherapy has shown efficacy in various neoplasms, such as small cell lung cancer and Merkel cell carcinoma. Although immunotherapy's effectiveness is more limited in NENs, combining immune checkpoint inhibitors with other therapeutic strategies like chemotherapy or targeted therapies could improve outcomes. Additionally, identifying predictive immune biomarkers could enhance patient selection. Our objective was to review the current evidence of immunotherapy in NENs, covering efficacy results and potential predictive biomarkers. A raise in the incidence of NENs is expected. Therefore, the identification of new therapeutic strategies, such as immunotherapy, remains crucial. To date, immune checkpoint inhibitors as monotherapy have shown modest activity in unselected NENs. Although immunotherapy combos (plus another immune agents or chemotherapy, among others) are potentially more active than single agents, this has not been uniformly confirmed, even in high-grade NENs. Other immunotherapeutic strategies under development include bispecific antibodies, targeting specific tumor antigens like DLL3, and cell therapy. Currently, no predictive immune biomarkers are available to guide clinical decisions. A comprehensive tumor molecular profiling approach needs to be developed for the selection of patients with NEN who could potentially benefit from immunotherapy. Ideally, clinical trials should incorporate this tumor molecular profiling to identify predictive biomarkers and improve efficacy. Achieving this goal requires an international collaborative effort. [ABSTRACT FROM AUTHOR]

Simple Summary: The armamentarium of first-line systemic therapy for patients with unresectable non-small cell lung cancer (NSCLC) has been rapidly expanding over the past two decades. Currently, about 50% of patients with NSCLC do not need chemotherapy as first-line treatment. For these patients, molecularly targeted therapy and immune checkpoint inhibitor therapy have significantly improved progression-free survival and overall survival with favorable toxicity profiles. Patient demographics and clinical features are not sufficient for the selection of these treatments. An unmet need of precision oncology is to select the most appropriate therapeutic regimen with maximal efficacy and minimal unwanted toxicity for individual patients with NSCLC based on the assessment of their molecular and immune biomarkers at diagnosis. In this review, we summarize the current data and propose a practical algorithm for implementing precision biomarker testing at diagnosis and selecting the most appropriate first-line systemic therapy for patients with unresectable, advanced, or metastatic NSCLC. First-line systemic therapy for patients with advanced or metastatic non-small cell lung cancer (NSCLC) has rapidly evolved over the past two decades. First, molecularly targeted therapy for a growing number of gain-of-function molecular targets has been shown to improve progression-free survival (PFS) and overall survival (OS) with favorable toxicity profiles compared to platinum-containing chemotherapy and can be given as first-line systemic therapy in ~25% of patients with NSCLC. Actionable genetic alterations include EGFR, BRAF V600E, and MET exon 14 splicing site-sensitizing mutations, as well as ALK-, ROS1-, RET-, and NTRK-gene fusions. Secondly, inhibitors of programmed cell death protein 1 or its ligand 1 (PD-1/L1) such as pembrolizumab, atezolizumab, or cemiplimab monotherapy have become a standard of care for ~25% of patients with NSCLC whose tumors have high PD-L1 expression (total proportion score (TPS) ≥50%) and no sensitizing EGFR/ALK alterations. Lastly, for the remaining ~50% of patients who are fit and whose tumors have no or low PD-L1 expression (TPS of 0–49%) and no sensitizing EGFR/ALK aberrations, platinum-containing chemotherapy with the addition of a PD-1/L1 inhibitor alone or in combination of a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor improves PFS and OS compared to chemotherapy alone. The objectives of this review are to summarize the current data and perspectives on first-line systemic treatment in patients with unresectable NSCLC and propose a practical algorithm for implementing precision biomarker testing at diagnosis. [ABSTRACT FROM AUTHOR]

Many studies aim to detect the early phase of dementia. One of the major ways to achieve this is to identify corresponding biomarkers, particularly immune blood biomarkers. The objective of this study was to identify such biomarkers in patients with mild cognitive impairment (MCI) in an experiment that included cognitive training. A group of patients with MCI diagnoses over the age of 65 participated in the study (n = 136). Measurements of cognitive functions (using the Mini-Mental State Examination scale and Montreal Cognitive Assessment) and determination of 27 serum biomarkers were performed twice: on the first visit and on the second visit, one year after the cognitive training. APOE genotypes were also determined. Concentrations of EGF (F = 17; p = 0.00007), Eotaxin (F = 7.17; p = 0.008), GRO (F = 13.42; p = 0.0004), IL-8 (F = 8.16; p = 0.005), MCP-1 (F = 13.46; p = 0.0001) and MDC (F = 5.93; p = 0.016) increased after the cognitive training in MCI patients. All these parameters except IL-8 demonstrated a weak correlation with other immune parameters and were poorly represented in the principal component analysis. Differences in concentrations of IP-10, FGF-2, TGFa and VEGF in patients with MCI were associated with APOE genotype. Therefore, the study identified several immune blood biomarkers that could potentially be associated with changes in cognitive function. [ABSTRACT FROM AUTHOR]

Simple Summary: Future reproduction methods for boosting crucial traits will likely be influenced by the proportion of genetic and phenotypic variances. Using PCR-DNA sequencing, the variations in the nucleotide sequences of the immunological genes between healthy buffaloes and buffaloes suffering from inflammatory reproductive disorders were discovered. When buffaloes experienced inflammatory reproductive disorders, they were more likely to express the examined genes. The molecular alterations may, therefore, provide crucial information about the relationships between the physiologies of the various reproductive pathways and help diagnose inflammatory postpartum disorders. The immunological genes that may interact with inflammatory postpartum diseases in Italian buffaloes were examined in this study. A total number of 120 female Italian buffaloes (60 normal and 60 with inflammatory reproductive diseases) were employed. Each buffalo's jugular vein was pierced to get five milliliters of blood. To obtain whole blood and extract DNA and RNA, the blood was placed within tubes containing sodium fluoride or EDTA anticoagulants. The immunological (IKBKG, LGALS, IL1B, CCL2, RANTES, MASP2, HMGB1, and S-LZ) genes' nucleotide sequence differences between healthy buffaloes and buffaloes affected by inflammatory reproductive diseases were found by employing PCR-DNA sequencing. According to Fisher's exact test (p ˂ 0.01), there were noticeably different probabilities of all major nucleotide changes spreading among buffalo groups with and without reproductive problems. Buffaloes were significantly more likely to express the examined genes when they had inflammatory reproductive diseases. The outcomes might support the significance of these markers' nucleotide variations and gene expression patterns as indicators of the prevalence of inflammatory reproductive disorders and provide a workable buffalo management policy. [ABSTRACT FROM AUTHOR]

Although immunotherapy has proved to be a very efficient therapeutic strategy for many types of tumors, the results for pancreatic cancer (PC) have been very poor. Indeed, chemotherapy remains the standard treatment for this tumor in the advanced stage. Clinical data showed that only a small portion of PC patients with high microsatellite instability/mismatch repair deficiency benefit from immunotherapy. However, the low prevalence of these alterations was not sufficient to lead to a practice change in the treatment strategy of this tumor. The main reasons for the poor efficacy of immunotherapy probably lie in the peculiar features of the pancreatic tumor microenvironment in comparison with other malignancies. In addition, the biomarkers usually evaluated to define immunotherapy efficacy in other cancers appear to be useless in PC. This review aims to describe the main features of the pancreatic tumor microenvironment from an immunological point of view and to summarize the current data on immunotherapy efficacy and immune biomarkers in PC. [ABSTRACT FROM AUTHOR]

Simple Summary: Pneumonia is a commonly encountered problem in small ruminant medicine practice that negatively affects goat breeding. Some of the limitations of the conventional approaches used by animal breeders to promote animal health may be overcome with the use of molecular genetic tools. Using PCR-DNA sequencing in pneumonia-affected and -resistant Baladi goats, SNPs associated with pneumonia resistance/susceptibility were found in the SLC11A1, CD-14, CCL2, TLR1, TLR7, TLR8, TLR9, β defensin, SP110, SPP1, BP1, A2M, ADORA3, CARD15, IRF3, and SCART1 genes. These indicators' mRNA levels were different in both the healthy and affected goats. Therefore, to improve the effectiveness of animal selection for innate resistance, finding potential genes linked to pneumonia risk may be crucial. The effectiveness of breeding for inherent disease resistance in animals could be considerably increased by identifying the genes and mutations that cause diversity in disease resistance. One hundred and twenty adult female Baladi goats (sixty pneumonic and sixty apparently healthy) were used in this study. DNA and RNA were extracted from blood samples collected from the jugular vein of each goat. SLC11A1, CD-14, CCL2, TLR1, TLR7, TLR8, TLR9, β defensin, SP110, SPP1, BP1, A2M, ADORA3, CARD15, IRF3, and SCART1 SNPs that have been previously found to be associated with pneumonia resistance/susceptibility were identified via PCR-DNA sequencing. The pneumonic and healthy goats differed significantly, according to a Chi-square analysis of the discovered SNPs. The mRNA levels of the studied immune markers were noticeably greater in the pneumonic goats than in the healthy ones. The findings could support the significance of the use of immune gene expression profiles and nucleotide variations as biomarkers for the susceptibility/resistance to pneumonia and provide a practical management technique for Baladi goats. These results also suggest a potential strategy for lowering pneumonia in goats by employing genetic markers linked to an animal's ability to fend off infection in selective breeding. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) pathway has been shown to play a crucial role in several inflammatory conditions and host immune-inflammation status is related to tumor prognosis. This study aims to evaluate the prognostic significance of a four-gene inflammatory signature in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients treated with the EGFR inhibitor cetuximab plus chemotherapy. The inflammatory signature was assessed on 123 R/M HNSCC patients, enrolled in the multicenter trial B490 receiving first-line cetuximab plus platinum-based chemotherapy. The primary endpoint of the study was progression free survival (PFS), while secondary endpoints were overall survival (OS) and objective response rate (ORR). The patient population was subdivided into 3 groups according to the signature score groups. The four-genes-signature proved a significant prognostic value, resulting in a median PFS of 9.2 months in patients with high vs. 6.2 months for intermediate vs. 3.9 months for low values (p = 0.0016). The same findings were confirmed for OS, with median time of 18.4, 13.4, and 7.5 months for high, intermediate, and low values of the score, respectively (p = 0.0001). When ORR was considered, the signature was significantly higher in responders than in non-responders (p = 0.0092), reaching an area under the curve (AUC) of 0.65 (95% CI: 0.55–0.75). Our findings highlight the role of inflammation in the response to cetuximab and chemotherapy in R/M-HNSCC and may have translational implications for improving treatment selection. [ABSTRACT FROM AUTHOR]

Since no definitive cure for COVID-19 is available so far, one of the challenges against the disease is understanding the clinical features and the laboratory inflammatory markers that can differentiate among different severity grades of the disease. The aim of the present study is a comprehensive and longitudinal evaluation of SCD14-ST and other new inflammatory markers, as well as cytokine storm molecules and current inflammatory parameters, in order to define a panel of biomarkers that could be useful for a better prognostic prediction of COVID-19 mortality. SCD14-ST, as well as the inflammatory markers IL-6, IL-10, SuPAR and sRAGE, were measured in plasma-EDTA of ICU COVID-19 positive patients. In this longitudinal study, SCD14-ST resulted significantly higher in patients who eventually died compared to those who were discharged from the ICU. The results suggest that the new infection biomarker SCD14-ST, in addition to new generation inflammatory biomarkers, such as SuPAR, sRAGE and the cytokines IL-6 and IL-10, can be a useful prognostic tool associated with canonical inflammatory parameters, such as CRP, to predict SARS-CoV-2 outcome in ICU patients. [ABSTRACT FROM AUTHOR]

Visceral leishmaniasis is one of the deadliest parasitic diseases in the world and affects both humans and dogs. The host immune response to Leishmania infection plays a critical role in the evolution of canine visceral leishmaniasis (CVL) and consequently in the manifestation of clinical signs. The asymptomatic form of the disease is a major concern in the diagnosis of CVL and in the transmission control of Leishmania infection. Asymptomatic dogs are found in large proportions in endemic areas and are an unquantifiable source of infection. The present review analyzes the possible relationship between the activation of the antigen-specific immune response of the host and resistance or susceptibility to CVL. The review focuses on works that address the characterization of the humoral and cellular immune response profile, at both the functional and phenotypic levels, in infected dogs. Most studies relate the absence of clinical symptomatology to an increased proliferative response and a Th1 cytokine profile. Despite the numerous findings pointing to a differential immune response in asymptomatic dogs, the contradictory results reported in this review highlight the importance of establishing a precise clinical classification of the disease, performing more longitudinal studies, and including a higher number of animals in trials. [ABSTRACT FROM AUTHOR]

Simple Summary: In pancreatic cancer, immunotherapy and targeted therapies have not brought about the therapeutic revolution that has been observed in other malignancies. Among the reasons to explain this difference is the possibly crucial role played by the pancreatic tumor microenvironment, which has unique features and is different from that of other neoplasms. The aim of this review is to provide a comprehensive overview of the distinctive tumor immune microenvironment of pancreatic cancer and to summarize existing data about the use of immunotherapy and immune biomarkers in this cancer. The advent of immunotherapy and targeted therapies has dramatically changed the outcomes of patients affected by many malignancies. Pancreatic cancer (PC) remains one the few tumors that is not treated with new generation therapies, as chemotherapy still represents the only effective therapeutic strategy in advanced-stage disease. Agents aiming to reactivate the host immune system against cancer cells, such as those targeting immune checkpoints, failed to demonstrate significant activity, despite the success of these treatments in other tumors. In many cases, the proportion of patients who derived benefits in early-phase trials was too small and unpredictable to justify larger studies. The population of PC patients with high microsatellite instability/mismatch repair deficiency is currently the only population that may benefit from immunotherapy; nevertheless, the prevalence of these alterations is too low to determine a real change in the treatment scenario of this tumor. The reasons for the unsuccess of immunotherapy may lie in the extremely peculiar tumor microenvironment, including distinctive immune composition and cross talk between different cells. These unique features may also explain why the biomarkers commonly used to predict immunotherapy efficacy in other tumors seem to be useless in PC. In the current paper, we provide a comprehensive and up-to-date review of immunotherapy in PC, from the analysis of the tumor immune microenvironment to immune biomarkers and treatment outcomes, with the aim to highlight that simply transferring the knowledge acquired on immunotherapy in other tumors might not be a successful strategy in patients affected by PC. [ABSTRACT FROM AUTHOR]

Simple Summary: Biomarkers for cancer diagnosis, prognosis and prediction are important tools and an urgent need in precision medicine for pancreatic cancer. In recent years, many experimental and clinical studies aimed at identifying new biomarkers for pancreatic ductal adenocarcinoma. In the review, we summarized current investigations on using novel protein markers, cell-free DNA, metabolome compounds, immune and stroma signatures and microbiome compositions as biomarkers for pancreatic cancer. Our comprehensive overview shows that although there are new promising biomarkers, CA 19-9 remains currently the only regularly used and validated biomarker for pancreatic cancer in clinical routine. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a dismal prognosis that is frequently diagnosed at an advanced stage. Although less common than other malignant diseases, it currently ranks as the fourth most common cause of cancer-related death in the European Union with a five-year survival rate of below 9%. Surgical resection, followed by adjuvant chemotherapy, remains the only potentially curative treatment but only a minority of patients is diagnosed with locally resectable, non-metastatic disease. Patients with advanced disease are treated with chemotherapy but high rates of treatment resistance and unfavorable side-effect profiles of some of the used regimens remain major challenges. Biomarkers reflect pathophysiological or physiological processes linked to a disease and can be used as diagnostic, prognostic and predictive tools. Thus, accurate biomarkers can allow for better patient stratification and guide therapy choices. Currently, the only broadly used biomarker for PDAC, CA 19-9, has multiple limitations and the need for novel biomarkers is urgent. In this review, we highlight the current situation, recent discoveries and developments in the field of biomarkers of PDAC and their potential clinical applications. [ABSTRACT FROM AUTHOR]

It is estimated that pancreatic cancer will be the second leading cause of cancer-related deaths globally by 2030, highlighting the ongoing lack of effective treatment options for this devastating condition. There is a lack of reliable prognostic or predictive markers in pancreatic cancer to guide management decisions, whether for systemic chemotherapy, molecularly targeted therapies, or immunotherapies. To date, the results for targeted agents and immunotherapies in unselected populations of chemo-refractory pancreatic cancer have not met expectations. The reasons for this lack of efficacy of immunotherapy in pancreatic cancer are not completely understood. The challenges in pancreatic cancer include the physical barrier created by the dense desmoplastic stroma surrounding the tumor, chemokine-mediated exclusion of T cells, relatively poorer antigenicity compared to other solid tumors, paucity of infiltrating T cells within the tumor, ultimately leading to an immunosuppressive microenvironment. A better understanding of the role of inflammation in pancreatic cancer, its tumor microenvironment and individualized patient-related features, be they molecular, clinical or histopathological, would enable a more effective tailored approach to the management of pancreatic cancer. In this review, the role of inflammation, the immune tumor microenvironment and potential immune biomarkers in pancreatic cancer are explored. [ABSTRACT FROM AUTHOR]