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Pediatric acute myeloid leukemia (pedAML) is a childhood malignancy with relapse rates of approximately 30%. CD68, a macrophage marker involved in phagocytosis and macrophage recruitment, may contribute to AML biology. We analyzed expression using the TARGET database and performed survival analyses, mRNA/protein profiling, and functional assays in AML cell lines, pedAML samples, and cord blood samples. High transcript levels correlated with -rearrangements and inversion 16. Survival analysis showed that high predicted worse event-free survival, though not independently in a multivariate analysis. Flow cytometry confirmed higher CD68 expression in 7/8 pedAML samples compared to cord blood samples. Functionally, knockdown reduced proliferation and increased drug sensitivity, while overexpression promoted growth and resistance. Gene set enrichment analysis (GSEA) indicated enrichment of MAPK signaling, AP-1-mediated stress response, and epithelial-mesenchymal transition (EMT)/migration-associated pathways in -high models. Together, these findings suggest that CD68 contributes to a pro-tumorigenic and stress-adaptive phenotype in pedAML and may represent a biologically relevant therapeutic target.

Macrophages are an essential component of antitumor activity; however, the role of tumor‐associated macrophages (TAMs) in colorectal cancer (CRC) remains controversial. Here, we elucidated the role of TAMs in CRC progression, especially at the early stage. We assessed the TAM number, phenotype, and distribution in 53 patients with colorectal neoplasia, including intramucosal neoplasia, submucosal invasive colorectal cancer (SM‐CRC), and advanced cancer, using double immunofluorescence for CD68 and CD163. Next, we focused on the invasive front in SM‐CRC and association between TAMs and clinicopathological features including lymph node metastasis, which were evaluated in 87 SM‐CRC clinical specimens. The number of M2 macrophages increased with tumor progression and dynamic changes were observed with respect to the number and phenotype of TAMs at the invasive front, especially at the stage of submucosal invasion. A high M2 macrophage count at the invasive front was correlated with lymphovascular invasion, low histological differentiation, and lymph node metastasis; a low M1 macrophage count at the invasive front was correlated with lymph node metastasis. Furthermore, receiver operating characteristic curve analysis revealed that the M2/M1 ratio was a better predictor of the risk of lymph node metastasis than the pan‐, M1, or M2 macrophage counts at the invasive front. These results suggested that TAMs at the invasive front might play a role in CRC progression, especially at the early stages. Therefore, evaluating the TAM phenotype, number, and distribution may be a potential predictor of metastasis, including lymph node metastasis, and TAMs may be a potential CRC therapeutic target. We identified dynamic changes in the number and phenotype of tumor‐associated macrophages (TAMs) at the invasive front in colorectal cancer (CRC), especially at the stage of submucosal invasion. Furthermore, TAMs at the invasive front may play a role in CRC progression, especially in early stage CRC, ie, M1 macrophages at the invasive front may inhibit CRC progression, while M2 macrophages may promote CRC progression via EMT. Therefore, a marker comprising the phenotype, number, and distribution of TAMs may serve as a potential predictor of metastasis, including lymph node metastasis, and TAMs may be a potential therapeutic target in CRC.

A growing body of literature describes the anti-inflammatory, neuroprotective, and anti-epileptic properties of the cannabis sativa constituent cannabidiol, suggesting that it might play a useful role in the treatment of neurodegenerative diseases. Late infantile neuronal ceroid lipofuscinosis (CLN2 disease) is a rare pediatric neurodegenerative disorder resulting from an inherited dysfunction of the lysosome. CLN2 disease, and its representative animal models, display neuroimmune response, neuroinflammation, neurodegeneration, and epileptic seizures, and these symptoms are all touted as potential targets of cannabidiol therapeutic benefit. Here, we treated a valid model of CLN2 disease with long-term daily cannabidiol (300 mg/kg) from 1 month of age until disease end stage and evaluated epileptic seizures, lifespan, and markers of neuroimmune response. Chronic cannabidiol treatment significantly delayed or fully eliminated seizures in CLN2 model mice compared to those treated with vehicle only, and the treatment led to a non-significant extension of lifespan. These effects occurred in the absence of any therapeutic benefit to physiological markers of disease such as GFAP, CD68, and cytokine/chemokine reactivity. Taken together, we show that chronic treatment with cannabidiol confers significant anti-seizure benefit to the mouse model of CLN2 disease, and that it does not appear to do so by altering the inflammatory and neuroimmune markers traditionally used to track CLN2 disease progression.

SARS-CoV-2 has an affinity for binding to the human Angiotensin-converting enzyme 2 (ACE2) receptor through cleavage and conformational changes at the S1–S2 boundary and the receptor binding domain of the spike protein, which is also the most variable part of SARS-CoV-2. This study aimed to investigate the expression of Angiotensin-converting enzyme 2 (ACE2), spike protein, and CD68+ markers in placental tissue to demonstrate a possible correlation with the level of systemic oxidative stress biomarkers in patients who were infected with SARS-CoV-2 during pregnancy. A prospective clinical cohort study was designed to investigate the presence of CD68+ macrophages, ACE2, and spike proteins in placental tissue using immunohistochemical methods and to compare these results with oxidative stress from our previous study. Spike and CD68+ macrophages’ immunoreactivity were more pronounced in the placental tissue of patients from the SARS-CoV-2 group. Placental tissue spike protein and CD68+ immunoreactivity correlate with maternal and fetal Thiobarbituric Acid Reactive (TBARS) levels. This study has confirmed that spike protein expression in placental tissue is associated with the newborn’s stay in intensive neonatal care. Therefore, immunoreactivity analysis for the Spike antigen is important in detecting newborns at risk of early neonatal complications.

The current investigation aims to study the embryonic dermis formed in the early stages of development and identify the initial interstitial components of the dermis that serve as biological and structural scaffolds for the development of the dermal tissue. To investigate the dermal structure, the current study used morphological and immunological techniques. TCs identified by TEM. They had a cell body and unique podomeres and podoms. They formed a 3D network spread throughout the dermis. Homocellular contact established between them, as well as heterocellular contacts with other cells. Immunohistochemical techniques using specific markers for TCss CD34, CD117, and VEGF confirmed TC identification. TCs represent the major interstitial component in the dermal tissue. They established a 3D network, enclosing other cells and structures. Expression of VEGF by TC promotes angiogenesis. TCs establish cellular contact with sprouting endothelial cells. At the site of cell junction with TCs, cytoskeletal filaments identified and observed to form the pseudopodium core that projects from endothelial cells. TCs had proteolytic properties that expressed MMP-9, CD68, and CD21. Proteolytic activity aids in the removal of components of the extracellular matrix and the phagocytosis of degraded remnants to create spaces to facilitate the development of new dermal structures. In conclusion, TCs organized the scaffold for the development of future dermal structures, including fibrous components and skin appendages. Studying dermal TCs would be interested in the possibility of developing therapeutic strategies for treating different skin disorders and diseases.

Renal artery stenosis (RAS) caused by narrowing of arteries is characterized by microvascular damage. Macrophages are implicated in repair and injury, but the specific populations responsible for these divergent roles have not been identified. Here, we characterized murine kidney F4/80 + CD64 + macrophages in three transcriptionally unique populations. Using fate-mapping and parabiosis studies, we demonstrate that CD11b/c int are long-lived kidney-resident (KRM) while CD11c hi Mϕ, CD11c lo Mϕ are monocyte-derived macrophages. In a murine model of RAS, KRM self-renewed, while CD11c hi Mϕ and CD11c lo Mϕ increased significantly, which was associated with loss of peritubular capillaries. Replacing the native KRM with monocyte-derived KRM using liposomal clodronate and bone marrow transplantation followed by RAS, amplified loss of peritubular capillaries. To further elucidate the nature of interactions between KRM and peritubular endothelial cells, we performed RNA-sequencing on flow-sorted macrophages from Sham and RAS kidneys. KRM showed a prominent activation pattern in RAS with significant enrichment in reparative pathways, like angiogenesis and wound healing. In culture, KRM increased proliferation of renal peritubular endothelial cells implying direct pro-angiogenic properties. Human homologs of KRM identified as CD11b int CD11c int CD68 + increased in post-stenotic kidney biopsies from RAS patients compared to healthy human kidneys, and inversely correlated to kidney function. Thus, KRM may play protective roles in stenotic kidney injury through expansion and upregulation of pro-angiogenic pathways.

This study aimed to analyze the infiltration of tumor-associated macrophages (TAMs) in clear cell renal cell carcinoma (ccRCC) and to assess their Prognostic significance. This study involved a Cohort of 106 patients with ccRCC who underwent partial or radical nephrectomy. Immunohistochemistry (IHC) was employed to assess the expression of two distinct types of macrophages at various tissue locations. The diagnostic utility of CD68-positive (CD68 + ) and CD163-positive (CD163 + ) macrophages was determined via Kaplan–Meier with log-rank tests and Multivariable Cox regression. Compared with those in adjacent tissues, the numbers of CD68 + and CD163 + TAMs were significantly elevated in ccRCC tissues. Kaplan–Meier analysis demonstrated that high CD163 + TAM density was significantly associated with poorer overall survival (p = 0.006 in tumor nest, p = 0.043 in stroma), while CD68 + TAMs showed no significant prognostic value (p > 0.4 for all comparisons). Multivariable Cox regression confirmed CD163 + TAMs as independent prognostic factors after adjusting for tumor size and histological grade, with particularly strong association in tumor stroma (adjusted HR = 7.22, 95% CI 1.06–25.54, p = 0.003) compared to tumor nests (adjusted HR = 3.56, 95% CI 1.03–15.56, p = 0.045). TAMs, particularly the M2 subtype (CD163 + ), are identified as adverse prognostic factors for ccRCC patients. Those with a high density of M2 macrophages tend to have a poorer prognosis.

Obesity is characterized by chronic low-grade inflammation (meta-inflammation) and metabolic dysregulation. Adipose tissue acts as an immunometabolic organ, with macrophages playing a central role. This review examines inflammatory memory in adipose tissue, focusing on CD68+ macrophages and their role in cardiometabolic and cancer risk during weight cycling. (2) Narrative synthesis of evidence from immunology, obesitology, and oncology, with emphasis on macrophage polarization and signaling pathways. (3) Weight cycling induces persistent immune memory in adipose tissue, characterized by exaggerated macrophage responses upon weight regain. CD68+ macrophages contribute to extracellular matrix remodeling, tumor signaling, and metabolic dysfunction. Key mechanisms include PI3K/AKT/mTOR dysregulation, FOXO1/KLF10 axis impairment, and CREB-mediated transcription. This inflammatory memory promotes atherosclerosis progression, insulin resistance, and increased cancer risk, despite prior weight loss. (4) Macrophage-driven inflammatory memory represents a key mechanistic link between obesity, cardiometabolic disease, and cancer. Targeting meta-inflammation independent of body weight should be integral to future therapies.

Seroma formation is a frequent complication following mastectomy in the surgical treatment of breast cancer with profound consequences for the patients including possibly quality of life impairing implant complications. The pathogenesis remains unknown, leading to a lack of efficient preventive and curative strategies. The study’s objective was to determine whether the macrophage infiltration of the tumor microenvironment and surrounding adipose tissue at the time of primary surgery is associated with postoperative seroma development. The observational monocentric SerMa pilot study was conducted from 12/2019 to 12/2022. We included 91 breast cancer and 9 carcinoma in situ cases treated with mastectomy at the University Hospital Augsburg, Germany. Patients with previous malignancies, metastatic disease and known immunodeficiency were excluded. The patients underwent different mastectomy procedures with or without implant- or expander-based breast reconstruction. The study’s main outcome was seroma formation up to six months post-surgery, determined by clinical examination and fine needle aspiration of the seroma fluid if clinically necessary. Macrophage markers (CD68 and CD163) were immunohistochemically determined in formalin fixed paraffin-embedded slides containing the primary tumor and surrounding adipose tissue. Two groups were then formed as independent variables: cases with (seroma +) and without postoperative seroma formation (seroma-). Since all parameters in this study were not normally distributed, the non-parametric Mann–Whitney-U-test was used. A p-value < 0.05 was considered statistically significant. CD68 + cells (cases with seroma (seroma +): median = 90.7 cells, IQR = 62.5–130.5; cases without seroma (seroma-): median = 64.3 cells, IQR = 47.0–115-0, p = 0.036) and CD163 + cells (seroma + : median = 58.3 cells, IQR = 33.0–91.4; seroma-: median = 40.7 cells, IQR = 28.3–55.3, p = 0.027) in the tumor microenvironment and in the surrounding adipose tissue (CD68 + cells (seroma + : median = 8.0 cells, IQR = 5.3–11.0; seroma-: median = 4.7 cells, IQR = 3.0–10.0, p = 0.013), CD163 + cells (seroma + : median = 11.0 cells, IQR = 6.7–15.0; seroma-: median = 6.7 cells, IQR = 3.0–9.7, p = 0.016)) were significantly higher in cases with postoperative seroma formation compared to cases without. In the SerMa pilot study macrophage polarization within the primary tumor and surrounding adipose tissue was associated with post-operative seroma formation in breast cancer patients. This might be a suitable biomarker for predicting a higher risk of seroma formation.

The assessment of PD-L1 in lung cancer using the Tumour Proportion Score (TPS) is one of the cornerstones of immune-oncology, but it is open to inter- and intra-pathologist variation, particularly around the clinical thresholds of less than 1% and ⩾ 50%, which correspond to analytical thresholds less than 5% and between 40%-60%. In this paper we describe the development of a deep learn- ing (DL) tool to assist TPS calculation. To confirm ground truth values around the clinical thresholds, we used a validated multiplex immunfluorescence panel including PD-L1, CD68 and cytokeratin. Practically, the DL tool is designed to assist in highlighting cases about these thresholds around the 1% and 50% levels for manual review, and allowing a direct interpretation of inbetween scores. Us- ing such an assisted system, we highlight the potential use of such DL tools in providing a route to future clinical quantitation of tissue-based biomarkers.