is on the board of directors of Amgen and ThermoFisher Scientific, a co-founder of Dragonfly Therapeutics and T2 Biosystems, an SAB member of Dragonfly Therapeutics, SQZ Biotech, and Skyhawk Therapeutics and is president of Break Through Cancer. All rights reserved.ĭeclaration of interests T.J. Vaccination eliminated CCR6 + TCF1 + cells and dramatically improved the subdominant response, highlighting a strategy to optimally engage concurrent neoantigen responses against tumors.ĬCR6 CD8 T cell TCF1 Tc17 checkpoint blockade immunodominance lung cancer neoantigen vaccine.Ĭopyright © 2021 Elsevier Inc. Analysis of human samples and sequencing datasets revealed that CCR6 + TCF1 + cells exist across human cancers and are not correlated with ICB response. However, the subdominant T cell response did not preferentially benefit from ICB due to a dysfunctional subset of TCF1 + cells marked by CCR6 and Tc17 differentiation. T cells responding to subdominant antigens were enriched for a TCF1 + progenitor phenotype correlated with response to immune checkpoint blockade (ICB) therapy. In mouse lung adenocarcinoma, we found that immunodominance is established in tumors, wherein CD8 T cell expansion is predominantly driven by the antigen that most stably binds MHC. Electronic address: onĬD8 T cell responses against different tumor neoantigens occur simultaneously, yet little is known about the interplay between responses and its impact on T cell function and tumor control. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. 9 Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA Department of Oncologic Pathology, Dana Farber Cancer Institute, Boston, MA 02215, USA.Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA Genentech, 1 DNA Way, South San Francisco, CA 94080, USA. 7 Melanoma Disease Center, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA Center for Immuno-oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.6 Melanoma Disease Center, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA Center for Immuno-oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. 3 Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA Laboratory of Systems Pharmacology, Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.