病例报告：错配修复缺陷型心脏肉瘤对帕博利珠单抗的持久完全缓解：基因组特征分析

Sarcomas are traditionally considered "cold" tumors with poor response to immunotherapy.

However, evidence accumulating over the last years shows that immune checkpoint inhibitors (ICIs) may have a role in selected sarcoma patients according to predictive markers.

Here, we report the case of a woman diagnosed with a primary cardiac undifferentiated sarcoma. Following failure of standard first line chemotherapy, high-throughput sequencing (HTS) revealed a high tumor mutational burden (TMB), pathogenic mutations in FAT1 and NOTCH2 and a microsatellite instability (MSI)-associated signature. Immunohistochemistry confirmed mismatch repair-deficiency (MMRd) and abundant CD8+ tumor-infiltrating lymphocytes (TILs), in the absence of tertiary lymphoid structures.

The patient was, therefore, treated with the ICI pembrolizumab, reaching a complete response that continues to persist at last follow-up, more than seven years from initial diagnosis and nearly six years from initiation of ICI treatment.

This case illustrates the importance of performing HTS in rare sarcomas given the availability of efficient therapies, such as those for tumors displaying high TMB or MMRd/MSI. In agreement with other reports, it supports the contention that MMRd/MSI status and high numbers of TILs are valuable predictive markers of response to immunotherapy in sarcomas.