Section of Hematology and Oncology, Department of Internal Medicine, Wake Forest Baptist Medical Center, Winston Salem, North Carolina, USA.
Department of Cancer Biology, Wake Forest School of Medicine, Winston Salem, North Carolina, USA.
Cancer. 2022 Sep 1;128(17):3254-3264. doi: 10.1002/cncr.34333. Epub 2022 Jun 29.
Cellular and intrinsic markers of sarcoma immunogenicity are poorly understood. To gain insight into whether tumor-immune interactions correlate with clinical aggressiveness, the authors examined the prognostic significance of immune gene signatures in combination with tumor mutational burden (TMB) and cancer-testis antigen (CTA) expression.
RNA sequencing and clinical data of 259 soft tissue sarcomas from The Cancer Genome Atlas project were used to investigate associations between published immune gene signatures and patient overall survival (OS) in the contexts of TMB, as computed from whole-exome sequencing data, and CTA gene expression. Multivariate Cox proportional hazards regression models and log-rank tests were used to assess survival associations.
Immune signature scores that reflected in part the intratumoral abundance of cytotoxic T cells showed significant positive associations with OS. However, the prognostic power of the T-cell signatures was highly dependent on TMB-high status, consistent with protective effects of tumor-infiltrating T cells in tumors with elevated antigenicity. In TMB-low tumors, a signature of infiltrating plasma B cells was significantly and positively associated with OS, independent of T-cell signature status. Although tumor subtypes based on differential expression patterns of CTA genes showed different survival associations within leiomyosarcoma and myxofibrosarcoma histologies, neither CTA nor histologic subtype interacted with the T-cell-survival association.
Signatures of T-cell and plasma B-cell infiltrates were associated with a survival benefit in soft tissue sarcomas. TMB, but not CTA expression, influenced the prognostic power of T-cell-associated, but not plasma B-cell-associated, survival.
Clinical data and RNA analysis of 259 soft tissue sarcomas from The Cancer Genome Atlas project were used to investigate associations between five published gene immune cell expression signatures and survival in the context of tumor mutations. Activated T cells had a significant positive association with patient survival. Although high tumor mutation burden was associated with good survival, the prognostic power of T-cell signatures was highly dependent on tumor mutational status, consistent with protective effects of tumor-infiltrating T cells in tumors with high levels of antigens. In low tumor mutation-bearing tumors, plasma B cells were positively associated with survival.
肉瘤的细胞和内在免疫标志物尚未完全了解。为了深入了解肿瘤免疫相互作用是否与临床侵袭性相关，作者研究了免疫基因特征与肿瘤突变负担（TMB）和癌症睾丸抗原（CTA）表达相结合的预后意义。
利用癌症基因组图谱计划（The Cancer Genome Atlas project）中 259 例软组织肉瘤的 RNA 测序和临床数据，研究了发表的免疫基因特征与 TMB 相关的患者总生存期（OS）之间的相关性，TMB 是根据全外显子测序数据计算得出的，同时还研究了 CTA 基因表达。使用多变量 Cox 比例风险回归模型和对数秩检验评估生存相关性。
部分反映细胞毒性 T 细胞肿瘤内丰度的免疫特征评分与 OS 呈显著正相关。然而，T 细胞特征的预后能力高度依赖于 TMB-高状态，这与肿瘤内浸润 T 细胞在抗原性升高的肿瘤中具有保护作用一致。在 TMB-低肿瘤中，浸润性浆细胞的特征与 OS 呈显著正相关，独立于 T 细胞特征状态。尽管基于 CTA 基因差异表达模式的肿瘤亚型在平滑肌肉瘤和黏液纤维肉瘤组织学中表现出不同的生存相关性，但 CTA 或组织学亚型均未与 T 细胞生存相关性相互作用。
T 细胞和浆细胞浸润的特征与软组织肉瘤的生存获益相关。TMB 但不是 CTA 表达影响了与 T 细胞相关但不与浆细胞相关的生存的 T 细胞相关预后的预测能力。
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