Dataset Information

Paracrine Regulation and Immune System Pathways in the Inflammatory Tumor Microenvironment of Lung Cancer: Insights into Oncogenesis and Immunotherapeutic Strategies.

ABSTRACT: The intricate interplay between inflammatory processes and the tumor microenvironment (TME) in lung cancer has garnered increasing attention due to its implications for both oncogenesis and therapeutic strategies. In this review, we explore recent advances in understanding the paracrine regulation and immune system pathways within the inflammatory TME of lung cancer. We delve into the molecular mechanisms underpinning oncogenesis, highlighting the role of immune cell populations, cancer-associated fibroblasts, and endothelial cells, as well as their interactions through immune system pathways regulated in a paracrine pattern. Additionally, we discuss emerging immunotherapeutic strategies with a specific focus on the potential of leveraging the inflammatory TME through these pathways to enhance treatment efficacy in lung cancer.

SUBMITTER: Batrash F

PROVIDER: S-EPMC10969565 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Paracrine Regulation and Immune System Pathways in the Inflammatory Tumor Microenvironment of Lung Cancer: Insights into Oncogenesis and Immunotherapeutic Strategies.

Batrash Firas F Shaik Adnan A Rauf Rayaan R Kutmah Mahmoud M Zhang Jun J

Cancers 20240310 6

The intricate interplay between inflammatory processes and the tumor microenvironment (TME) in lung cancer has garnered increasing attention due to its implications for both oncogenesis and therapeutic strategies. In this review, we explore recent advances in understanding the paracrine regulation and immune system pathways within the inflammatory TME of lung cancer. We delve into the molecular mechanisms underpinning oncogenesis, highlighting the role of immune cell populations, cancer-associat ...[more]

PMID: 38539448

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Project description:BackgroundChordoma is a rare, invasive, and devastating bone malignancy of residual notochord tissue that arises at the skull base, sacrum, or spine. In order to maximize immunotherapeutic approaches as a potential treatment strategy in chordoma it is important to fully characterize the tumor immune microenvironment (TIME). Multispectral immunofluorescence (MIF) allows for comprehensive evaluation of tumor compartments, molecular co-expression, and immune cell spatial relationships. Here we implement MIF to define the myeloid, T cell, and natural killer (NK) cell compartments in an effort to guide rational design of immunotherapeutic strategies for chordoma.MethodsChordoma tumor tissue from 57 patients was evaluated using MIF. Three panels were validated to assess myeloid cell, T cell, and NK cell populations. Slides were stained using an automated system and HALO software objective analysis was utilized for quantitative immune cell density and spatial comparisons between tumor and stroma compartments.ResultsChordoma TIME analysis revealed macrophage infiltration of the tumor parenchyma at a significantly higher density than stroma. In contrast, helper T cells, cytotoxic T cells, and T regulatory cells were significantly more abundant in stroma versus tumor. T cell compartment infiltration more commonly demonstrated a tumor parenchymal exclusion pattern, most markedly among cytotoxic T cells. NK cells were sparsely found within the chordoma TIME and few were in an activated state. No immune composition differences were seen in chordomas originating from diverse anatomic sites or between those resected at primary versus advanced disease stage.ConclusionThis is the first comprehensive evaluation of the chordoma TIME including myeloid, T cell, and NK cell appraisal using MIF. Our findings demonstrate that myeloid cells significantly infiltrate chordoma tumor parenchyma while T cells tend to be tumor parenchymal excluded with high stromal infiltration. On average, myeloid cells are found nearer to target tumor cells than T cells, potentially resulting in restriction of T effector cell function. This study suggests that future immunotherapy combinations for chordoma should be aimed at decreasing myeloid cell suppressive function while enhancing cytotoxic T cell and NK cell killing.

Dataset Information

Paracrine Regulation and Immune System Pathways in the Inflammatory Tumor Microenvironment of Lung Cancer: Insights into Oncogenesis and Immunotherapeutic Strategies.

Publications

Paracrine Regulation and Immune System Pathways in the Inflammatory Tumor Microenvironment of Lung Cancer: Insights into Oncogenesis and Immunotherapeutic Strategies.

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