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J Immunol. 2019 Jun 15;202(12):3458-3467. doi: 10.4049/jimmunol.1801022. Epub 2019 Apr 29.

Identification of Neoantigen-Reactive Tumor-Infiltrating Lymphocytes in Primary Bladder Cancer.

Author information

1
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
2
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20982.
3
Genitourinary Malignancies Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and.
4
Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
5
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; Yong-Chen.Lu@nih.gov.

Abstract

Immune checkpoint inhibitors are effective in treating a variety of malignancies, including metastatic bladder cancer. A generally accepted hypothesis suggests that immune checkpoint inhibitors induce tumor regressions by reactivating a population of endogenous tumor-infiltrating lymphocytes (TILs) that recognize cancer neoantigens. Although previous studies have identified neoantigen-reactive TILs from several types of cancer, no study to date has shown whether neoantigen-reactive TILs can be found in bladder tumors. To address this, we generated TIL cultures from patients with primary bladder cancer and tested their ability to recognize tumor-specific mutations. We found that CD4+ TILs from one patient recognized mutated C-terminal binding protein 1 in an MHC class II-restricted manner. This finding suggests that neoantigen-reactive TILs reside in bladder cancer, which may help explain the effectiveness of immune checkpoint blockade in this disease and also provides a rationale for the future use of adoptive T cell therapy targeting neoantigens in bladder cancer.

PMID:
31036766
PMCID:
PMC6548619
[Available on 2020-06-15]
DOI:
10.4049/jimmunol.1801022

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