Persistent mutant oncogene specific T cells in two patients benefitting from anti-PD-1
Autor: | Qingfeng Zhu, Haidan Guo, Franco Verde, Hao Wang, Patrick M. Forde, Dung T. Le, Sune Justesen, Teniola Oke, Hongni Fan, Prerna Suri, Leslie Cope, Ludmila Danilova, Janis M. Taube, Anas H. Awan, Franck Housseau, Jennifer N. Durham, Hok Yee Chan, Nickolas Papadopoulos, Elizabeth D. Thompson, Bjarne Bartlett, Robert A. Anders, Nicholas Siegel, Victor E. Velculescu, Kellie N. Smith, John-William Sidhom, Laveet K. Aulakh, Kristen A. Marrone, Valsamo Anagnostou, Cynthia L. Sears, Joanne Riemer, Drew M. Pardoll, Luis A. Diaz, Brandon Luber, Ada J. Tam, Bert Vogelstein, Tricia R. Cottrell, Nicolas J. Llosa, Kenneth W. Kinzler, Julie R. Brahmer, William H. Sharfman, Jarushka Naidoo |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Cancer Research Lung Neoplasms Colorectal cancer T cell T-Lymphocytes Immunology Cell T cells Case Report Disease lcsh:RC254-282 B7-H1 Antigen 03 medical and health sciences 0302 clinical medicine Antineoplastic Agents Immunological Predictive biomarkers Checkpoint blockade Carcinoma Non-Small-Cell Lung medicine Immunology and Allergy Humans Oncogene Aged Pharmacology Neoantigens business.industry Correction Oncogenes medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Primary tumor 3. Good health Blockade 030104 developmental biology medicine.anatomical_structure Nivolumab Treatment Outcome Oncology 030220 oncology & carcinogenesis Mutation Cancer research Molecular Medicine DNA mismatch repair Female business Colorectal Neoplasms |
Zdroj: | Journal for ImmunoTherapy of Cancer, Vol 7, Iss 1, Pp 1-8 (2019) Journal for Immunotherapy of Cancer |
ISSN: | 2051-1426 |
Popis: | Background Several predictive biomarkers are currently approved or are under investigation for the selection of patients for checkpoint blockade. Tumor PD-L1 expression is used for stratification of non-small cell lung (NSCLC) patients, with tumor mutational burden (TMB) also being explored with promising results, and mismatch-repair deficiency is approved for tumor site-agnostic disease. While tumors with high PD-L1 expression, high TMB, or mismatch repair deficiency respond well to checkpoint blockade, tumors with lower PD-L1 expression, lower mutational burdens, or mismatch repair proficiency respond much less frequently. Case presentation We studied two patients with unexpected responses to checkpoint blockade monotherapy: a patient with PD-L1-negative and low mutational burden NSCLC and one with mismatch repair proficient colorectal cancer (CRC), both of whom lack the biomarkers associated with response to checkpoint blockade, yet achieved durable clinical benefit. Both maintained T-cell responses in peripheral blood to oncogenic driver mutations – BRAF-N581I in the NSCLC and AKT1-E17K in the CRC – years after treatment initiation. Mutation-specific T cells were also found in the primary tumor and underwent dynamic perturbations in the periphery upon treatment. Conclusions These findings suggest that T cell responses to oncogenic driver mutations may be more prevalent than previously appreciated and could be harnessed in immunotherapeutic treatment, particularly for patients who lack the traditional biomarkers associated with response. Comprehensive studies are warranted to further delineate additional predictive biomarkers and populations of patients who may benefit from checkpoint blockade. Electronic supplementary material The online version of this article (10.1186/s40425-018-0492-x) contains supplementary material, which is available to authorized users. |
Databáze: | OpenAIRE |
Externí odkaz: |