Search Results (497)

Despite targeting mainly the respiratory tract, SARS-CoV-2 disrupts T cell homeostasis in ways that may explain both acute lethality and long-term immunological consequences. In this study, we aimed to evaluate the T-cell-mediated chain of immunity and formation of TCR via TREC assessment in COVID-19 and long COVID (LC). For this study, we collected 231 blood samples taken from patients with acute COVID-19 (n = 71), convalescents (n = 51), people diagnosed with LC (n = 63), and healthy volunteers (n = 46). With flow cytometry, we assessed levels of CD4+ and CD8+ minor T cell subpopulations (i.e., naïve, central and effector memory cells (CM and EM), Th1, Th2, Th17, Tfh, Tc1, Tc2, Tc17, Tc17.1, and subpopulations of effector cells (pE1, pE2, effector cells)). Additionally, we measured TREC levels. We found distinct changes in immune cell distribution—whilst distribution of major subpopulations of T cells was similar between cohorts, we noted that COVID-19 was associated with a decrease in naïve Th and CTLs, an increase in Th2/Tc2 lymphocyte polarization, an increase in CM cells, and a decrease in effector memory cells 1,3, and TEMRA cells. LC was associated with naïve CTL increase, polarization towards Th2 population, and a decrease in Tc1, Tc2, Em2, 3, 4 cells. We also noted TREC correlating with naïve cells subpopulations. Our findings suggest ongoing immune dysregulation, possibly driven by persistent antigen exposure or tissue migration of effector cells. The positive correlation between TREC levels and naïve T cells in LC patients points to residual thymic activity. The observed Th2/Th17 bias supports the hypothesis that LC involves autoimmune mechanisms, potentially driven by molecular mimicry or loss of immune tolerance. Full article

Background: Regulatory T cells (Tregs) are the main suppressor cells that maintain immune tolerance and prevent autoimmunity. Changes in Treg number or function are implicated in a wide range of autoimmune and inflammatory (AI/I) diseases, with or without underlying inborn errors of immunity (IEI). Understanding the phenotypic profiles of Treg subsets and their associations with immune dysregulation is crucial to identifying potential robust and holistic biomarkers for disease activity. Methods: We examined peripheral blood mononuclear cells from 40 patients diagnosed with various autoimmune/inflammatory diseases, including those with genetically confirmed inborn errors of immunity (IEIs), and compared these samples to those from 38 healthy controls of the same age. Utilizing multiparametric flow cytometry, we measured multiple Treg sub-populations and investigated their correlations with lymphocyte subset profiles and the diversity of autoantibodies. We applied advanced statistical and machine learning techniques, such as t-SNE, k-means clustering, and ROC analysis, to analyze immunophenotypic patterns in the patients. Results: Among all Treg sub-populations, only CD4⁺CD127^lowCD25^highFOXP3⁺ Tregs showed a significant decrease in patients compared to healthy controls (p < 0.05), while other Treg phenotypes did not differ. FOXP3 expression showed reduced intensity in patients and demonstrated diagnostic potential (AUC = 0.754). Notably, this Treg subset negatively correlated with CD19⁺ B cell percentages and positively correlated with the diversity of circulating autoantibodies. Unsupervised clustering revealed three distinct immunophenotypic profiles, highlighting heterogeneity among patients and underlining FOXP3-centered immune dysregulation. Conclusions: Our results presented that patients have an impairment in the CD4⁺CD127^lowCD25^highFOXP3⁺ regulatory T cell subset, which is identified by significantly decreased frequency and decreased expression of FOXP3. Immunological heterogeneity among patients was further uncovered by unsupervised clustering, highlighting the critical role that FOXP3-centered regulatory failure plays in the pathophysiology of illness. The combined evaluation of these three immunological factors, centered around FOXP3, holds promise as an integrative tool for monitoring disease progression across various autoimmune and immunodeficient contexts. Full article

Scientific evidence has suggested, in most cases, that nullity of the GSTM1 and GSTT1 genes is associated with worse pathological outcomes and viral infections. In this sense, the main objective of this work was to determine the genotypic frequencies of GSTM1 and GSTT1 polymorphisms in individuals with HIV and to establish a possible relationship with CD4+ T lymphocyte count. This was a cross-sectional study, with a quantitative approach, composed of 182 HIV-positive patients. To detect GSTM1 and GSTT1 polymorphisms by the multiplex polymerase chain reaction (PCR), oral mucosa samples were collected. Regarding genotypic frequencies, GST nullity was high in the population, being 97.5% and 97.6%, respectively, for GSTM1− and GSTT1−. Although there was no association between the GST polymorphism and the viral load and CD4+ T lymphocyte counts at diagnosis, when related to the current CD4+ count, the isolated and combined null alleles, GSTT1 (ORadj: 0.219; p = 0.004), GSTM1 (ORadj: 0.219; p = 0.004), and GSTM1/T1 (ORadj: 0.219; p = 0.004), were defined as factors favorable to a minimum CD4+ T lymphocyte count of 350 cells. Therefore, this study demonstrated a probable relationship between the GSTT1 and GSTM1 genetic polymorphisms and HIV. Full article

Platelet-rich plasma (PRP) has become an increasingly valuable biologic approach for personalized regenerative medicine because of its potent anti-inflammatory/healing effects. It is thought to be an excellent source of growth factors that can promote tissue healing and lessen fibrosis. Although this treatment has demonstrated effectiveness in numerous disease areas, its impact on pulmonary fibrosis (PF) caused by silver nanoparticles (AgNPs) via its antiapoptotic effects remains to be explored. AgNPs were synthesized biologically by Bacillus megaterium ATCC 55000. AgNP characterization was carried out via UV–Vis spectroscopy, X-ray diffraction (XRD), dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) imaging to reveal monodispersed spheres with a mean diameter of 45.17 nm. A total of 48 male Wistar rats divided into six groups, with 8 rats per group, were used in the current study on the basis of sample size and power. The groups used were the PRP donor, control, AgNP, AgNP + PRP, AgNP + dexamethasone (Dexa) rat groups, and a recovery group. Body weights, hydroxyproline (HP) levels, and CASP3 and TWIST1 gene expression levels were assessed. H&E and Sirius Red staining were performed. Immunohistochemical studies for inducible nitric oxide synthase (iNOS) and cluster of differentiation 68 (CD68) with histomorphometry were conducted. A significant reduction in body weight (BWt) was noted in the AgNP group compared with the AgNP + PRP group (p < 0.001). HP, CASP3, and TWIST1 expression levels were significantly increased by AgNPs but decreased upon PRP (p < 0.001) treatment. Compared with those in the control group, the adverse effects of AgNPs included PF, lung alveolar collapse, thickening of the interalveolar septa, widespread lymphocytic infiltration, increased alveolar macrophage CD68 expression, and iNOS positivity in the cells lining the alveoli. This work revealed that PRP treatment markedly improved the histopathological and immunohistochemical findings observed in the AgNP group in a manner comparable to that of the Dexa. In conclusion, these results demonstrated the therapeutic potential of PRP in a PF rat model induced via AgNPs. This study revealed that PRP treatment significantly improved the histopathological and immunohistochemical alterations observed in the AgNP-induced group, with effects comparable to those of the Dexa. In conclusion, these findings highlight the therapeutic potential of PRP in a rat model of AgNP-induced PF. Full article

Emerging evidence highlights the role of the tumor microbiome, including Fusobacterium nucleatum (Fn), in a wide range of gastrointestinal cancers. Fn purportedly contributes to tumorigenesis by activating oncogenic pathways and modulating immune responses. Although the prevalence and impact of Fn has been extensively studied in colorectal cancer, no previous systematic or in situ studies have been performed in appendiceal cancer (AC). The aim of this study was to evaluate the prevalence and association of Fn density in AC with clinical factors and oncologic outcomes. Archival tissue from 54 patients with AC was assessed for Fn density using RNA in situ hybridization. Clinicopathological variables were obtained for each case through electronic medical record review, and the immune microenvironment was characterized in each case using immunohistochemistry to quantify CD3+ and CD8+ T lymphocytes and M1-/M2-like tumor-associated macrophages. In AC, Fn density was associated with patient age, tumor grade, and histologic subtype. Fn was negatively associated with CD3+ and CD8+ T lymphocytes and positively associated with M2-like TAMs in low-grade AC. Interestingly, tumor Fn content was associated with better overall and progression-free survival, even when controlling for tumor grade. In this exploratory study, we found that Fn is prevalent in AC. Fn is associated with a number of clinical, pathologic, immunologic, and prognostic variables in AC that are distinct from the corresponding observed associations in colorectal cancer. Further research is warranted to validate these findings and explore the mechanistic contributions of Fn to AC pathogenesis or immune response. Full article

Background/Objectives: Intrahepatic cholangiocarcinoma (iCCA) is subclassified into small- and large-duct types. Small-duct-type iCCAs are associated with a better prognosis, and each subclassification requires different surgical strategies. The efficacy of chemotherapy, including immune checkpoint inhibitors, may vary between subclassifications. However, there are no reports on tumor immune microenvironment (TIME) analyses based on iCCA subclassifications. This study investigated subclassification-specific TIMEs in iCCAs for the purpose of establishing appropriate pharmacotherapy. Methods: A total of 131 resected iCCA cases were analyzed, comprising 73 tumors classified as small-duct-type and 58 as large-duct-type based on pathological evaluation. Immunohistochemical analyses targeting CD8, PD-1, PD-L1, CTLA-4, and S100 protein (a dendritic cell [DC] marker) were performed to investigate the immune-cell status in each subclassification. Results: Large-duct-type iCCA had a significantly higher CD8 expression in tumor-infiltrating cells than small-duct-type ICC. However, the expression of other molecules did not significantly differ between the two tumor types. The proportion of tumors with a high level of S100 protein expression (DC-high group) in tumor-infiltrating cells was significantly higher in small-duct-type ICCs than in large-duct-type iCCAs (30% vs. 1.7%). In small-duct-type iCCAs, the expression levels of CD8, PD-1, PD-L1, and CTLA-4 were significantly higher in the DC-high group than in the DC-low group. Conclusions: We revealed subclassification-specific TIMEs in iCCAs. A subset of small-duct-type iCCAs exhibited strong DC infiltration. In these patients, the tumors may establish an immunosuppressive TIME to evade antitumor immunity triggered by DC-mediated antigen presentation. These findings may contribute to the development of tailored pharmacotherapy for each iCCA subclassification. Full article

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. Full article

Luminal B breast cancer (LBBC) represents an aggressive, high-grade ER+ disease, associated with a high proliferation rate, higher mutation burden, and higher probability of eliciting the immune response. Clinical and pathological data from 89 patients of stage II-III, triple-negative (TN), and luminal B-like BC (LB-like BC) were included in the analysis. All patients were submitted to neoadjuvant chemotherapy (NACT). Quantitative and qualitative evaluations of TILs (Tumor-Infiltrating Lymphocytes) were performed on tissue microarrays constructed from pretreatment core-needle biopsy tumor specimens. The proportion of stromal TILs, CD8, CD4, and PD-L1 positive (+) immune cells (IC), as well as the number of FOXP3, CTLA4, and HSP-70+ IC, was observed concerning tumor immunophenotype, traditional clinicopathological prognostic factors, and tumor response to NACT. There was no statistically significant difference in the proportion of stromal TILs between the LB-like and TNBC (p = 0.344) cohorts. However, a higher CD4/CD8 ratio was associated with the TNBC biology (p = 0.018) and within the LB-like BC cohort with a high proliferation index and metastatic nodal involvement (p = 0.045, p = 0.015). Within the LB-like BC cohort, a higher expression of PD-L1 and HSP70+ IC was associated with a high proliferation index of tumor cells (p = 0.018, p = 0.040), massive metastatic nodal involvement (p = 0.002, p = 0.026), and higher stages of disease (p = 0.004, p = 0.042). Better response to NACT was associated with higher numbers of HSP70+ IC and higher proportions of CD8+ cells within the LB-like BC cohort (p = 0.045, p = 0.012). Routine evaluation of immune markers and HSP70 may help identify high-risk patients of LB-like breast cancer who would have a better response to NACT. Full article

CD300 family members are immunoglobulin superfamily receptors that regulate immune cell function through either activating or inhibitory signals. Among them, CD300a is a prototypical inhibitory receptor, highly expressed in both myeloid and lymphoid lineages, and plays a pivotal role in the pathogenesis of inflammation and tumor immunity. CD300a transduces inhibitory signals in several immune cells—including mast cells, eosinophils, monocytes, dendritic cells (DCs), neutrophils, and natural killer (NK) cells—by recruiting SHP-1 phosphatase to immunoreceptor tyrosine-based inhibitory motifs (ITIMs) and suppressing activation pathways such as Toll-like receptor (TLR)-MyD88 and FcεRI signaling. Recent studies suggest that tumor cells may hijack CD300a-associated pathways to establish an immunosuppressive microenvironment that facilitates immune evasion, tumor survival, and potentially metastatic spread. Proposed mechanisms include reduced DC-mediated type I interferon (IFN) production, diminished NK cell cytotoxicity, and negative regulation of mast cell– and eosinophil-dependent anti-tumor responses. Although some of these findings are derived from in vivo models, the cumulative evidence positions CD300a as a critical immune checkpoint in tumor-associated immune regulation. In addition to its established roles in hematologic malignancies—including chronic lymphocytic leukemia, acute lymphoblastic leukemia, and acute myeloid leukemia—CD300a has also been implicated in modulating tumor-associated immune responses in other pathological contexts. While most studies emphasize its immune cell–mediated effects, emerging evidence suggests that CD300a may directly influence tumor progression by regulating immune homeostasis, intracellular signaling, and tumor microenvironment interactions. Collectively, these findings establish CD300a as a pleiotropic immunoregulatory molecule in both hematologic and non-hematologic malignancies, underscoring the need to further explore its broader relevance and therapeutic potential in cancer immunology. Full article

Hypoxia, a low-oxygen state, is a common feature of solid tumors. MCP1 (CCL2) is a small cytokine that is closely related to hypoxia and has a positive effect on tumor development. Hypoxia causes resistance to various treatments for solid tumors and the evasion of cancer immune surveillance by lymphocytes. Natural killer (NK) cells are innate lymphocytes that play an important role in cancer development, particularly in the liver. First, it was found that the incubation of HCC in hypoxia (2–5% O₂) significantly increased the production of several inflammatory cytokines, including MCP1, compared to that of normal oxygen (20% O₂). Subsequently, blocking MCP1 with an anti-MCP1 antibody in HCC cultures inhibited the growth and migration of HCC cells in vitro and in vivo. This was associated with a decrease in the expression of HIF-1α/STAT3 in HCC under hypoxia. Furthermore, blocking MCP1 in HCC cell cultures under hypoxia significantly increased the chemotaxis and activation of NK-92 cells against HCC cells. MCP1 blockade in HCC cell cultures under hypoxia induced a shift in NK cells to the CD56^+dim population and an increase in the expression of the activation receptors NKG2D and NKp44. In conclusion, modulation of MCP1 could enhance NK activity against hypoxic HCC cells. Full article

Background: It has yet to be determined whether the immunocytological profile of the bronchoalveolar lavage (BAL) in respiratory post-COVID syndrome (PCS) reflects the risk of persistent interstitial lung disease (ILD), including pulmonary fibrosis. In this study, we aimed to assess the prognostic value of the BAL cytoimmunologic profile in PCS-related ILD. Materials and Methods: We enrolled 58 non-smoking patients with a history of COVID-19 and new-onset ILD, divided into PCS remission and PCS persistence groups based on clinical data, including repeated computed tomography and pulmonary function tests. We phenotyped BAL major T cell subsets, immune checkpoints (including programmed cell death-1, PD1), and markers of Th1/Th2/Th17 polarization. Results: The PCS groups compared to the control showed increased total cell, lymphocyte, and neutrophil counts and a high BAL neutrophil:lymphocyte ratio (NLR). PCS persistence compared to the controls presented an increased neutrophil count (26 [17–36] vs. 2.6 [1.9–5.4] 10³/mL, median [Q1–Q3], p < 0.001) and percentage, BAL NLR (0.77 [0.26–1.63] vs. 0.21 [0.17–0.31], p < 0.0001), CD8+PD1+ cell percentage (43.5 [34–60.5] vs. 24.5 [22–44]%, p = 0.045), and a decreased CD4:CD8 ratio. A high percentage of CD4+CD196+CD183 cells (relevant to Th17 activity, 6.2 [2.0–9.4] vs. 1.2 [0.7–2.7]%, p = 0.02) and increased BAL supernatant elevated IL-8 levels (62.5 [16–243] vs. 10.9 [3.44–32] pg/mL, p = 0.002) were found in the PCS persistence vs. control groups. In the total PCS group, predicted values of Vital Capacity (VC) [16–243] and Diffusing Lung Capacity for CO (DLCO) correlated negatively with BAL NLR; VC correlated negatively with BAL CD8+PD1+; and DLCO correlated positively with the CD4:CD8 ratio. Conclusions: Worse prognosis in PCS is associated with higher BAL NLR, BAL neutrophilia, an elevated percentage of CD8+PD1+ lymphocytes, and a decline in the CD4:CD8 ratio. Th17 cells and IL-8 participate in lung PCS persistence. Full article

Goldfish (Carassius auratus) gills function as both respiratory and immune-regulatory organs, integrating neuroendocrine and immune responses to environmental stimuli. This study explores the spatial organization and interaction of neuroendocrine cells (NECs) and immune cells within goldfish gills using confocal immunohistochemistry and transmission electron microscopy. NECs, identified near blood capillaries and nerve fibers, highlight their role in environmental sensing and physiological regulation. These cells express serotonin (5-HT), a neurotransmitter critical for neuroimmune communication. Two distinct macrophage subsets were observed: iNOS-positive macrophages, concentrated in the basal epithelium, suggest a pro-inflammatory role, whereas 5-HT-positive macrophages, dispersed in the subepithelium, likely contribute to immune modulation. The co-localization of MHC-II and CD68 in macrophages further supports an active antigen-processing system in the gills. Ultrastructural analysis revealed diverse immune cells, including rodlet cells, telocytes, and lymphocytes, within the gill epithelium. Telocytes formed intricate networks with immune cells, highlighting their role in immune coordination and tissue homeostasis. These findings provide new insights into the neuroimmune interactions in fish gills, contributing to a broader understanding of aquatic immune systems and environmental adaptability. Full article

Backgrounds and objective: Disorders in the stomatognathic system and otorhinolaryngologic manifestations are frequently observed in individuals living with HIV. Ear, neck, and throat (ENT) signs and symptoms often serve as critical markers of treatment failure, particularly in the advanced stages of HIV infection. This article aims to evaluate and consolidate recent developments in the treatment and management of otorhinolaryngological manifestations in HIV-positive patients. Materials and methods: We carried out a retrospective clinical investigation of patients admitted with HIV/AIDS in the northeastern region of Romania, hospitalized in the “St. Parascheva” Clinical Hospital of Infectious Diseases in Iasi. We followed the viro-immunological status correlated with patients’ otolaryngology and dental symptomatology, aiming to emphasize the comorbidities of HIV/AIDS cases. The study period spanned from 1 January 2020 to 30 November 2024. Results: There were a total of 552 recorded cases of oropharyngeal manifestations in patients with HIV. They were more frequent in men (358 cases, 64.85%) than women (194 cases, 35.15%). The majority of cases were young adults, aged 30 to 39 years, comprising 255 patients (46.19%), and most cases (36.85%) had CD4+ T-lymphocyte values between 200 and 499 cells/μL. The most frequent diagnosis was oral candidiasis, recorded in 335 male and 174 female cases (509, 92.21% total). Other notable conditions included gingivitis/periodontitis, sinusitis/rhinosinusitis, mastoiditis, and dental abscesses, albeit at lower frequencies. Notably, antifungal therapy with fluconazole was the most frequently employed treatment, followed by aminopenicillins and fluoroquinolones. With respect to the antiretroviral treatment, 83.69% of cases were prescribed a single-pill regimen. Conclusions: The key to the management of HIV-positive patients is a multidisciplinary approach, including an ENT specialist and access to antiretroviral therapy. Full article

Early and appropriate diagnosis of soft-tissue sarcomas (STSs) is hampered by their relatively low prevalence and sometimes unusual clinical appearance. It takes a comprehensive diagnostic work-up to differentiate between different types of soft-tissue sarcomas. Determining tumor margins by preoperative imaging is important, especially in order to preserve the affected limb and improve quality of life. Misjudgment of tumor margins may increase or decrease the stage of soft-tissue sarcoma and thus influence the patient’s prognosis. The applicability of conventional MRI alone for determining the tumor margin is limited. Additional information regarding the peritumoral tissue, particularly at the cellular level, can be obtained via diffusion-weighted imaging (DWI). However, there are not many publications on employing DWI to evaluate tumor margin infiltration in soft-tissue sarcoma patients. Because the immune system plays a variety of roles during oncogenesis, it can occasionally be difficult to distinguish between tumor invasion and the presence of a reactive inflammatory infiltrate. Clarifying the predictive importance of lymphocyte infiltration in soft-tissue sarcomas was the goal of this investigation. We examined the correlations between expression of CD4, CD8, and CD34 and tumor margin infiltration observed on a DWI sequence. CD4, CD8, and CD34 marker positivity was linked to soft-tissue sarcomas that were less aggressive and did not invade the tumor margins, indicating a higher survival percentage for these individuals. Full article

Background and Objectives: Innate and adaptive immune responses serve a crucial role in neoplasms. The interaction of immune cells with the neoplastic tissue influences tumor behavior, resulting in either pro-tumorigenic or anti-tumorigenic effects. However, the prognostic significance of the tumor immune microenvironment (TIME) in synovial sarcoma (SS) remains poorly studied. This study aimed to analyze the TIME of SS to determine its impact on the prognosis by examining the intratumoral lymphocytic and macrophagic infiltrate and its potential correlation with survival and recurrence. Methods: We conducted a retrospective observational study of 49 fusion-confirmed SS cases collected from two different institutions. We obtained clinical and follow-up data, and SSs were histologically classified according to WHO criteria. Immunohistochemical analysis, including of CD163, CD68, CD3, CD8, and CD20, was conducted in tissue microarrays using an analog scale. We examined the whole-slide tissue for the 23 cases with sufficient material available and then assessed the positive area by scanning the slides and analyzing the images using QuPath (0.4.4, Belfast, Northern Ireland) to calculate the positive area in an immune hotspot. We correlated the expression of these markers with clinical outcomes. A log-rank test and Kaplan–Meyer curves were used as appropriate (significance: p ≤ 0.05). Results: The most frequent morphological subtype was monophasic (59.6%), followed by biphasic (26.9%) and undifferentiated (7%). The mean disease specific survival (DSS) was 55.3 months, with a median of 33 months. The median overall survival (OS) was 50 months (range: 2–336 months). Both evaluation methods showed a good correlation for all antibodies, with Chi-square values of p < 0.05. All cases showed variable amounts of CD163-positive macrophages. The cases that showed a higher density of CD163-positive macrophages in whole-slide images subjected to digital analysis demonstrated an improved OS and DSS on Kaplan–Meier curves. Cases with lower CD8 and CD3 positivity showed a tendency toward faster progression and a slightly worse prognosis. Conclusions: The tumor immune microenvironment in sarcomas is a complex system that requires further investigation to fully understand its impact on tumorigenesis and patient clinical outcomes. Our results demonstrate that a higher amount of intratumoral CD163-positive macrophage infiltrate is associated with an increased OS and DSS. Our findings show that digital pathology is more precise than subjective quantitative analysis. Full article