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Persistent mutant oncogene specific T cells in two patients benefitting from anti-PD-1
- Source :
- Journal for ImmunoTherapy of Cancer, Vol 7, Iss 1, Pp 1-8 (2019), Journal for Immunotherapy of Cancer
- Publication Year :
- 2019
- Publisher :
- BMJ Publishing Group, 2019.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 20511426
- Volume :
- 7
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal for ImmunoTherapy of Cancer
- Accession number :
- edsair.doi.dedup.....fde77c99e032427f14a5fba99a381eba