Distinct immunological mechanisms of CTLA-4 and PD-1 blockade revealed by analyzing TCR usage in blood lymphocytes

Lidia Robert; Christina Harview; Ryan Emerson; Xiaoyan Wang; Stephen Mok; Blanca Homet; Begonya Comin-Anduix; Richard C Koya; Harlan Robins; Paul C Tumeh; Antoni Ribas

doi:10.4161/onci.29244

Distinct immunological mechanisms of CTLA-4 and PD-1 blockade revealed by analyzing TCR usage in blood lymphocytes

Oncoimmunology. 2014 Jun 25:3:e29244. doi: 10.4161/onci.29244. eCollection 2014.

Authors

Affiliations

¹ Department of Medicine (Division of Hematology-Oncology); University of California Los Angeles (UCLA); Los Angeles, CA USA.
² Department of Medicine (Division of Dermatology); University of California Los Angeles (UCLA); Los Angeles, CA USA.
³ Fred Hutchinson Cancer Research Center; Seattle, WA USA ; Adaptive Biotechnologies; Seattle, WA USA.
⁴ Department of Medicine (Division of Hematology-Oncology); University of California Los Angeles (UCLA); Los Angeles, CA USA ; Department of Medicine (Statistics core); University of California Los Angeles (UCLA); Los Angeles, CA USA.
⁵ Department of Surgery (Division of Surgical-Oncology); University of California Los Angeles (UCLA); Los Angeles, CA USA.
⁶ Department of Surgery (Division of Surgical-Oncology); University of California Los Angeles (UCLA); Los Angeles, CA USA ; Jonsson Comprehensive Cancer Center (JCCC); University of California Los Angeles (UCLA); Los Angeles, CA USA.
⁷ Department of Medicine (Division of Hematology-Oncology); University of California Los Angeles (UCLA); Los Angeles, CA USA ; Department of Surgery (Division of Surgical-Oncology); University of California Los Angeles (UCLA); Los Angeles, CA USA ; Jonsson Comprehensive Cancer Center (JCCC); University of California Los Angeles (UCLA); Los Angeles, CA USA.

Abstract

Targeting immune inhibitory receptors has brought excitement, innovation and hope to cancer patients. Our recent work revealed the immunological effects of blocking the CTLA4 and PD-1 immune checkpoints on T cell receptor usage among peripheral blood cells, and further uncovers how the expansion of the T cell repertoire matches the immunotoxicity profile of the therapy.

Keywords: CTLA-4; MK-3475; PBMC; PD-1; TCR; Tremelimumab; sequencing.

Abstract

Grants and funding