In:
Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-10-21)
Abstract:
Chordoma 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. Methods Chordoma 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. Results Chordoma 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. Conclusion This 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.
Type of Medium:
Online Resource
ISSN:
2234-943X
DOI:
10.3389/fonc.2022.1012058
DOI:
10.3389/fonc.2022.1012058.s001
DOI:
10.3389/fonc.2022.1012058.s002
DOI:
10.3389/fonc.2022.1012058.s003
DOI:
10.3389/fonc.2022.1012058.s004
DOI:
10.3389/fonc.2022.1012058.s005
DOI:
10.3389/fonc.2022.1012058.s006
DOI:
10.3389/fonc.2022.1012058.s007
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2649216-7
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