Two cases of intrahepatic cholangiocellular carcinoma with high insertion-deletion ratios that achieved a complete response following chemotherapy combined with PD-1 blockade

Autor: Xianrong Lv, Minghao Sui, Xun Wang, Yu Li, Qiang Xu, Ying Luo, Tao Wan, Guan Wang, Bingyang Hu, Hongguang Wang, Xianlei Xin, Shichun Lu, Yanshuang Cheng
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Cancer Research
medicine.medical_treatment
Programmed Cell Death 1 Receptor
PD-1 blockade
Combination immunotherapy
Case Report
Gastroenterology
Cholangiocarcinoma
0302 clinical medicine
Antineoplastic Agents
Immunological
INDEL Mutation
Renal cell carcinoma
Positron Emission Tomography Computed Tomography
Antineoplastic Combined Chemotherapy Protocols
Immunology and Allergy
RC254-282
Intrahepatic cholangiocarcinoma
biology
Melanoma
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Middle Aged
Immunohistochemistry
Magnetic Resonance Imaging
Treatment Outcome
Oncology
030220 oncology & carcinogenesis
Whole-exome sequencing
Molecular Medicine
Female
medicine.medical_specialty
Immunology
03 medical and health sciences
Internal medicine
medicine
Biomarkers
Tumor
PTEN
Humans
Indel
Aged
Neoplasm Staging
Pharmacology
Chemotherapy
business.industry
Immunotherapy
medicine.disease
Blockade
030104 developmental biology
biology.protein
business
Progressive disease
Zdroj: Journal for Immunotherapy of Cancer
Journal for ImmunoTherapy of Cancer, Vol 7, Iss 1 (2019)
ISSN: 2051-1426
Popis: Background Insertion–deletion mutations (indels) may generate more tumour-specific neoantigens with high affinity to major histocompatibility complex class I. A high indel ratio is also related to a good response to programmed death-1 (PD-1) checkpoint blockade in melanoma and renal cell carcinoma. However, the correlation between a high indel ratio and the immunotherapy response in intrahepatic cholangiocarcinoma (ICC) is unknown. Case presentation Two patients with relapsed ICC at stage IIIb were treated with PD-1 blockade combined with chemotherapy. After 7 and 4 months of chemotherapy and PD-1 blockade (3 and 15 cycles, and 5 and 6 cycles, respectively), magnetic resonance imaging and positron emission tomography with computed tomography imaging showed that both patients achieved a complete response (CR), which has lasted up to nearly 16 and 13 months to date, respectively. Whole-exome sequencing and immunohistochemistry analysis showed that both patients had cancers with microsatellite stability (MSS) and mismatch repair (MMR) proficiency, weak PD-L1 expression, and a tumour mutation burden (TMB) of 2.95 and 7.09 mutations/Mb, respectively. Patient 2 had mutations of TP53 and PTEN that are known to confer sensitivity to immunotherapy, and the immunotherapy-resistant mutation JAK2, whereas patient 1 had no known immunotherapy response-related mutations. However, the indel ratios of the two patients (48 and 66.87%) were higher than the median of 12.77% determined in a study of 71 ICC patients. Moreover, comparison to six additional ICC patients who showed a partial response, stable disease, or progressive disease after PD-1 blockade treatment alone or in combination with chemotherapy demonstrated no difference in PD-L1 expression, TMB, MSI, and MMR status from those of the two CR patients, whereas the indel frequency was significantly higher in the CR patients. Conclusions These two cases suggest that indels might be a new predictor of PD-1 blockade response for ICC patients beside PD-L1 expression, TMB, MSI, and dMMR, warranting further clinical investigation. Electronic supplementary material The online version of this article (10.1186/s40425-019-0596-y) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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