Paradigms on Immunotherapy Combinations with Chemotherapy

被引:269
作者
Salas-Benito, Diego [1 ,2 ]
Perez-Gracia, Jose L. [1 ,2 ]
Ponz-Sarvise, Mariano [1 ,2 ]
Rodriguez-Ruiz, Maria E. [1 ,2 ]
Martinez-Forero, Ivan [3 ]
Castanon, Eduardo [1 ,2 ]
Lopez-Picazo, Jose M. [1 ,2 ]
Sanmamed, Miguel F. [1 ,2 ,4 ,5 ,6 ]
Melero, Ignacio [2 ,4 ,5 ,6 ,7 ]
机构
[1] Clin Univ Navarra, Oncol Dept, Pamplona, Spain
[2] Clin Univ Navarra, Clin Trials Unit, Pamplona, Spain
[3] MSD, Clin Res, Madrid, Spain
[4] Univ Navarra, Ctr Med Appl Res CIMA, Pamplona, Spain
[5] Navarra Inst Hlth Res IDISNA, Pamplona, Spain
[6] Biomed Res Network Oncol CIBERONC, Pamplona, Spain
[7] Clin Univ Navarra, Immunol Dept, Pamplona, Spain
基金
欧盟地平线“2020”;
关键词
PEMBROLIZUMAB PLUS CHEMOTHERAPY; SQUAMOUS-CELL CARCINOMA; 1ST-LINE 1L TREATMENT; SUPPORTIVE CARE BSC; REGULATORY T-CELLS; PHASE-III TRIAL; UROTHELIAL CARCINOMA; BREAST-CANCER; SUPPRESSOR-CELLS; NAB-PACLITAXEL;
D O I
10.1158/2159-8290.CD-20-1312
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Checkpoint inhibitors are being added to standard-of-care chemotherapy in multiple clinical trials. Success has been reported in non-small and small cell lung carcinomas and urothelial, head and neck, gastric, and esophageal cancers, and promising results are already available in triple-negative breast and pancreatic malignancies. The potential mechanisms of synergy include immunogenic tumor cell death, antiangiogenesis, selective depletion of myeloid immunosuppressive cells, and lymphopenia, which reduces regulatory T cells and makes room for proliferation of effector T cells. However, chemotherapy regimens have not been optimized for such combinations, perhaps explaining some recent clinical trial disappointments. Approaches to make the most of chemo-immunotherapy include neoadjuvant and adjuvant schemes. Significance: Immunotherapy of cancer based on PD-1/PD-L1 blockade has prompted a revolution in cancer clinical management. Evidence in phase III clinical trials already supports combinations of immunotherapy with standard-of-care chemotherapy for a number of malignant diseases. This review focuses on such evidence and provides an overview of the potential synergistic mechanisms of action and the opportunities to optimize chemoimmunotherapy regimens.
引用
收藏
页码:1353 / 1367
页数:15
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