1. PD-1 directed immunotherapy alters Tfh and humoral immune responses to seasonal influenza vaccine
- Author
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Ramin Sedaghat Herati, David A. Knorr, Laura A. Vella, Luisa Victoria Silva, Lakshmi Chilukuri, Sokratis A. Apostolidis, Alexander C. Huang, Alexander Muselman, Sasikanth Manne, Oliva Kuthuru, Ryan P. Staupe, Sharon A. Adamski, Senthil Kannan, Raj K. Kurupati, Hildegund C. J. Ertl, Jeffrey L. Wong, Stylianos Bournazos, Suzanne McGettigan, Lynn M. Schuchter, Ritesh R. Kotecha, Samuel A. Funt, Martin H. Voss, Robert J. Motzer, Chung-Han Lee, Dean F. Bajorin, Tara C. Mitchell, Jeffrey V. Ravetch, and E. John Wherry
- Subjects
Adult ,Influenza Vaccines ,Vaccination ,Immunology ,Humans ,Immunology and Allergy ,Seasons ,T-Lymphocytes, Helper-Inducer ,Immunity, Humoral - Abstract
Anti-programmed death-1 (anti-PD-1) immunotherapy reinvigorates CD8 T cell responses in patients with cancer but PD-1 is also expressed by other immune cells, including follicular helper CD4 T cells (Tfh) which are involved in germinal centre responses. Little is known, however, about the effects of anti-PD-1 immunotherapy on noncancer immune responses in humans. To investigate this question, we examined the impact of anti-PD-1 immunotherapy on the Tfh-B cell axis responding to unrelated viral antigens. Following influenza vaccination, a subset of adults receiving anti-PD-1 had more robust circulating Tfh responses than adults not receiving immunotherapy. PD-1 pathway blockade resulted in transcriptional signatures of increased cellular proliferation in circulating Tfh and responding B cells compared with controls. These latter observations suggest an underlying change in the Tfh-B cell and germinal centre axis in a subset of immunotherapy patients. Together, these results demonstrate dynamic effects of anti-PD-1 therapy on influenza vaccine responses and highlight analytical vaccination as an approach that may reveal underlying immune predisposition to adverse events.
- Published
- 2022