Multi-spectral immunofluorescence evaluation of the myeloid, T cell, and natural killer cell tumor immune microenvironment in chordoma may guide immunotherapeutic strategies.
Multi-spectral immunofluorescence evaluation of the myeloid, T cell, and natural killer cell tumor immune microenvironment in chordoma may guide immunotherapeutic strategies.
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DOI：
10.3389/fonc.2022.1012058
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发表时间：
2022
影响因子：
4.7
通讯作者：
London Jr, Nyall R.
中科院分区：
文献类型：
--
作者：
Lopez, Diana C.;Robbins, Yvette L.;Kowalczyk, Joshua T.;Lassoued, Wiem;Gulley, James L.;Miettinen, Markku M.;Gallia, Gary L.;Allen, Clint T.;Hodge, James W.;London Jr, Nyall R.
关键词：
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. 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. 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. 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.
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影响因子：
22.7
作者：
Li T;Li X;Zamani A;Wang W;Lee CN;Li M;Luo G;Eiler E;Sun H;Ghosh S;Jin J;Murali R;Ruan Q;Shi W;Chen YH
通讯作者：
Chen YH
影响因子：
3.7
作者：
Kong LQ;Zhu XD;Xu HX;Zhang JB;Lu L;Wang WQ;Zhang QB;Wu WZ;Wang L;Fan J;Tang ZY;Sun HC
通讯作者：
Sun HC
DOI：
10.1016/j.urolonc.2014.02.007
发表时间：
2014-08-01
影响因子：
2.7
作者：
Sjodahl, Gottfrid;Lovgren, Kristina;Hoglund, Mattias
通讯作者：
Hoglund, Mattias
DOI：
10.1073/pnas.0408197102
发表时间：
2005-01-11
影响因子：
11.1
作者：
Chen, ML;Pittet, MJ;Khazaie, K
通讯作者：
Khazaie, K
影响因子：
5.8
作者：
Duan, Wanru;Zhang, Boyan;Chen, Zan
通讯作者：
Chen, Zan