Diverse immune environments in human lung tuberculosis granulomas assessed by quantitative multiplexed immunofluorescence

Abengozar-Muela, Marta; Villalba-Esparza, María; García-Ros, David; Vásquez, Cindy Estefanía; Echeveste, José; Idoate, Miguel A.; Lozano, Marı́a D.; Melero, Ignacio; Andrea, Carlos de

doi:10.1038/s41379-020-0600-6

Cited by 38 publications

(60 citation statements)

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“…A multiplex immunofluorescence panel was used to enable simultaneous examination of several cellular markers, including the phagocytic cell marker CD68 of macrophages, CD3 + and CD8 + T cells, and CD20 + B lymphocytes. Multiplex immunofluorescence development and validation workflow and protocols were implemented as previously described ( Schalper et al, 2019 ; Abengozar-Muela et al, 2020 ; Salas-Benito et al, 2021 ). Briefly, 5-μm sections of FFPE tissue were deparaffinized and antigen retrieval was performed using DAKO PT-Link heat-induced antigen retrieval with low pH (pH 6) or high pH (pH 9) target retrieval solution (DAKO).…”

Section: Methodsmentioning

confidence: 99%

“…We applied this technology to evaluate the complex immune environment of the ITF of uADC and uLMS. A previously developed and validated multiplex immunolabeling panel was used to simultaneously assess the phagocytic cell marker CD68 of macrophages, CD3 + and CD8 + T cells, and CD20 + B lymphocytes in a single FFPE tissue ( Abengozar-Muela et al, 2020 ; Salas-Benito et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Characterizing the Invasive Tumor Front of Aggressive Uterine Adenocarcinoma and Leiomyosarcoma

Sanegre

Eritja

Andrea

et al. 2021

Front. Cell Dev. Biol.

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The invasive tumor front (the tumor–host interface) is vitally important in malignant cell progression and metastasis. Tumor cell interactions with resident and infiltrating host cells and with the surrounding extracellular matrix and secreted factors ultimately determine the fate of the tumor. Herein we focus on the invasive tumor front, making an in-depth characterization of reticular fiber scaffolding, infiltrating immune cells, gene expression, and epigenetic profiles of classified aggressive primary uterine adenocarcinomas (24 patients) and leiomyosarcomas (11 patients). Sections of formalin-fixed samples before and after microdissection were scanned and studied. Reticular fiber architecture and immune cell infiltration were analyzed by automatized algorithms in colocalized regions of interest. Despite morphometric resemblance between reticular fibers and high presence of macrophages, we found some variance in other immune cell populations and distinctive gene expression and cell adhesion-related methylation signatures. Although no evident overall differences in immune response were detected at the gene expression and methylation level, impaired antimicrobial humoral response might be involved in uterine leiomyosarcoma spread. Similarities found at the invasive tumor front of uterine adenocarcinomas and leiomyosarcomas could facilitate the use of common biomarkers and therapies. Furthermore, molecular and architectural characterization of the invasive front of uterine malignancies may provide additional prognostic information beyond established prognostic factors.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterizing the Invasive Tumor Front of Aggressive Uterine Adenocarcinoma and Leiomyosarcoma

Sanegre

Eritja

Andrea

et al. 2021

Front. Cell Dev. Biol.

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“…The procedure allows therefore to explore not only a single cell population but also the cellular composition and the relationship between different immune cell types and/or immune cells and tumor cells in different fields. A recent study (51) has characterized different types of immune cells in human tuberculosis granulomas using ultra-fast cycling for multiplexed cellular fluorescence imaging. This supports the promising usefulness of the procedure to explore the role of the tumor microenvironment (TME) and its dynamic changes related to cancer progression and/or the effect of treatment.…”

Section: Future Perspectives and Conclusionmentioning

confidence: 99%

PD-L1 in Cytological Samples: A Review and a Practical Approach

et al. 2021

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With a growing number of predictive biomarkers needed to manage patients with non-small cell lung cancer (NSCLC), there has been a paradigm shift in care and handling of diagnostic samples. Among the various testing methods, immunohistochemistry (IHC) is the most cost- effective and widely available. Furthermore, over the past decade immunotherapy has emerged as one of the most promising cancer treatments. In this scenario IHC is the most used testing method available for PDL-1/PD1 immunotherapy. Several monoclonal antibodies targeting programmed death 1 (PD-1)/programmed death ligand-1 (PD-L1) pathways have been integrated into standard-of-care treatments of a wide range of cancer types, once provided evidence of PD-L1 expression in tumor cells by immunohistochemistry (IHC). Since currently available PD-L1 assays have been developed on formalin-fixed paraffin embedded (FFPE) histological specimens, a growing body of research is being dedicated to confirm the feasibility of applying PDL-1 assays also to cytological samples. Albeit promising results have been reported, several important issues still need to be addressed. Among these are the type of cytological samples, pre-analytical issues, cyto-histological correlation, and inter-observer agreement. This review briefly summarizes the knowledge of the role of cytopathology in the analysis of PD-L1 by immunocytochemistry (ICC) and future directions of cytopathology in the immunotherapy setting.

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“…A total of 162 patients providing 230 spots were included in the analysis. Multiplex immunofluorescence (IF) validation workflows and protocols have been implemented, as previously described [56,57]. Briefly, 4 µm sections of FFPE tissue from TMAs were deparaffinized, and antigen retrieval was performed using heat-induced antigen retrieval with low pH (pH 6) or high pH (pH 9) solutions.…”

Section: Tma Construction Immunohistochemistry and Immunofluorescencementioning

confidence: 99%

Proteomic Analysis of Low-Grade, Early-Stage Endometrial Carcinoma Reveals New Dysregulated Pathways Associated with Cell Death and Cell Signaling

López-Janeiro

Ruz-Caracuel

Ramon-Patino

et al. 2021

Cancers

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Low-grade, early-stage endometrial carcinoma (EC) is the most frequent malignant tumor of the uterine corpus. However, the molecular alterations that underlie these tumors are far from being fully understood. The purpose of this study is to describe dysregulated molecular pathways from EC patients. Sixteen samples of tumor tissue and paired healthy controls were collected and both were subjected to mass spectrometry (MS)/MS proteomic analysis. Gene ontology and pathway analysis was performed to discover dysregulated pathways and/or proteins using different databases and bioinformatic tools. Dysregulated pathways were cross-validated in an independent external cohort. Cell signaling, immune response, and cell death-associated pathways were robustly identified. The SLIT/ROBO signaling pathway demonstrated dysregulation at the proteomic and transcriptomic level. Necroptosis and ferroptosis were cell death-associated processes aberrantly regulated, in addition to apoptosis. Immune response-associated pathways showed a dominance of innate immune responses. Tumor immune infiltrates measured by immunofluorescence demonstrated diverse lymphoid and myeloid populations. Our results suggest a role of SLIT/ROBO, necroptosis, and ferroptosis, as well as a prominent role of innate immune response in low-grade, early-stage EC. These results could guide future research in this group of tumors.

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Diverse immune environments in human lung tuberculosis granulomas assessed by quantitative multiplexed immunofluorescence

Cited by 38 publications

References 40 publications

Characterizing the Invasive Tumor Front of Aggressive Uterine Adenocarcinoma and Leiomyosarcoma

Characterizing the Invasive Tumor Front of Aggressive Uterine Adenocarcinoma and Leiomyosarcoma

PD-L1 in Cytological Samples: A Review and a Practical Approach

Proteomic Analysis of Low-Grade, Early-Stage Endometrial Carcinoma Reveals New Dysregulated Pathways Associated with Cell Death and Cell Signaling

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