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具有恶性胸膜间皮瘤的超长缓解期患者的分子和免疫学特征，该患者最初接受了派姆单抗治疗，随后进行了再挑战。

Molecular and immunological features of a prolonged exceptional responder with malignant pleural mesothelioma treated initially and rechallenged with pembrolizumab.

机构信息

Drug Development Unit, Royal Marsden Hospital/ Institute of Cancer Research, Sutton, UK

Drug Development Unit, Royal Marsden Hospital/ Institute of Cancer Research, Sutton, UK.

出版信息

J Immunother Cancer. 2020 Mar;8(1). doi: 10.1136/jitc-2020-000713.

DOI:10.1136/jitc-2020-000713
PMID:32169873
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7069263/
Abstract

BACKGROUND

This case represents an exceptional response to pembrolizumab in a patient with epithelioid mesothelioma with a further response on rechallenge.

CASE PRESENTATION

A 77-year-old woman with advanced epithelioid mesothelioma extensively pretreated with chemotherapy demonstrated a prolonged response of 45 months to 52 cycles of pembrolizumab. On rechallenge with pembrolizumab, further disease stability was achieved. Serial biopsies and analysis by immunohistochemistry and immunofluorescence demonstrated marked immune infiltration and documented the emergency of markers of immune exhaustion. Whole exome sequencing demonstrated a reduction in tumor mutational burden consistent with subclone elimination by immune checkpoint inhibitor (CPI) therapy. The relapse biopsy had missense mutation in BTN2A1.

CONCLUSION

This case supports rechallenge of programme death receptor 1 inhibitor in cases of previous CPI sensitivity and gives molecular insights.

摘要

背景

本例代表了对顺铂治疗上皮样间皮瘤患者的异常反应，并且在重新挑战时再次出现反应。

病例介绍

一名 77 岁的女性患有晚期上皮样间皮瘤，经过广泛的化疗预处理，对 52 个周期的顺铂治疗有长达 45 个月的反应。在重新接受顺铂治疗时，进一步实现了疾病稳定。连续活检以及免疫组化和免疫荧光分析显示明显的免疫浸润，并记录了免疫衰竭标志物的出现。全外显子组测序显示肿瘤突变负担减少，这与免疫检查点抑制剂（CPI）治疗导致亚克隆消除一致。复发活检显示 BTN2A1 有错义突变。

结论

本病例支持在先前 CPI 敏感的情况下重新挑战程序性死亡受体 1 抑制剂，并提供了分子见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de0d/7069263/babfd14dd0d7/jitc-2020-000713f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de0d/7069263/e452c89cc7fa/jitc-2020-000713f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de0d/7069263/739308dfd102/jitc-2020-000713f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de0d/7069263/aa880a57df45/jitc-2020-000713f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de0d/7069263/babfd14dd0d7/jitc-2020-000713f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de0d/7069263/e452c89cc7fa/jitc-2020-000713f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de0d/7069263/739308dfd102/jitc-2020-000713f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de0d/7069263/aa880a57df45/jitc-2020-000713f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de0d/7069263/babfd14dd0d7/jitc-2020-000713f04.jpg

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