Objective Analysis and Clinical Significance of the Spatial Tumor-Infiltrating Lymphocyte Patterns in Non-Small Cell Lung Cancer.
Objective Analysis and Clinical Significance of the Spatial Tumor-Infiltrating Lymphocyte Patterns in Non-Small Cell Lung Cancer.
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非小细胞肺癌空间肿瘤浸润淋巴细胞模式的客观分析及临床意义。
DOI：
10.1158/1078-0432.ccr-23-2457
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Schalper,KurtA
中科院分区：
文献类型：
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作者：
LopezdeRodas,Miguel;Wang,Yvonne;Peng,Gang;Gu,Jianlei;Mino-Kenudson,Mari;Riess,JonathanW;Velcheti,Vamsidhar;Hellmann,Matthew;Gainor,JustinF;Zhao,Hongyu;Schalper,KurtA
目的研究淋巴细胞在肿瘤床中的空间排列（例如，免疫浸润、免疫排斥、免疫沙漠）反映不同的免疫逃避机制并与免疫治疗结果相关。然而，支持这些协会的数据是缺乏和有限的缺乏一个明确的定义淋巴细胞浸润模式和主观性质的病理学为基础的approaches.Experimental DesignWe使用多重免疫荧光研究主要肿瘤浸润淋巴细胞（TIL）亚群与单细胞分辨率在基线全组织切片样本从非小细胞肺癌患者接受免疫检查点抑制剂（ICI）。使用基于病理学家的定性方法和肿瘤/间质组织中TIL密度比的客观分析来分析空间TIL模式。不同的TIL markets.ResultsThe的空间模式与结果的关联进行了研究，使用定性评估的CD 8 +TIL模式的分析确定了突出的局限性，包括存在的广泛的表型内的大多数肿瘤和有限的关联与结果。利用客观的方法来分类非小细胞肺癌显示存在至少三个亚组，与使用视觉模式定义的亚组部分重叠。使用这种策略，一部分“免疫排斥样”肿瘤病例显示出明显更差的结果，表明对ICI的敏感性降低;然而，这些结果需要验证。其他TIL子集的分析显示出不同的结果，强调了空间TIL模式评价和市场integration.ConclusionsOur结果的机会选择的标记的相关性确定了与定性空间TIL模式评价的主要挑战。我们设计了一种新的客观策略，以克服其中一些具有强大生物标志物潜力的限制。
PurposeThe spatial arrangement of lymphocytes in the tumor bed (e.g., immune infiltrated, immune excluded, immune desert) is expected to reflect distinct immune evasion mechanisms and to associate with immunotherapy outcomes. However, data supporting these associations are scant and limited by the lack of a clear definition for lymphocyte infiltration patterns and the subjective nature of pathology-based approaches.Experimental DesignWe used multiplexed immunofluorescence to study major tumor-infiltrating lymphocyte (TIL) subsets with single-cell resolution in baseline whole-tissue section samples from NSCLC patients treated with immune checkpoint inhibitors (ICI). The spatial TIL patterns were analyzed using a qualitative pathologist-based approach, and an objective analysis of TIL density ratios in tumor/stromal tissues. The association of spatial patterns with outcomes was studied for different TIL markers.ResultsThe analysis of CD8+TIL patterns using qualitative assessment identified prominent limitations including the presence of a broad spectrum of phenotypes within most tumors and limited association with outcomes. The utilization of an objective method to classify NSCLCs showed the existence of at least three subgroups with partial overlap with those defined using visual patterns. Using this strategy, a subset of cases with “immune excluded-like” tumors showed prominently worse outcomes, suggesting reduced sensitivity to ICI; however, these results need to be validated. The analysis for other TIL subsets showed different results, underscoring the relevance of the marker selected for spatial TIL pattern evaluation and opportunities for market integration.ConclusionsOur results identified major challenges associated with the qualitative spatial TIL pattern evaluation. We devised a novel objective strategy to overcome some of these limitations that has strong biomarker potential.