A Phenotypic Signature That Identifies Neoantigen-reactive T Cells in Fresh Human Lung Cancers

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2022 Apr 22

PMID 35452604

Authors

Ken-Ichi Hanada

Chihao Zhao

Raul Gil-Hoyos

Jared J Gartner

Christopher Chow-Parmer

Frank J Lowery

Sri Krishna

Todd D Prickett

Scott Kivitz

Maria R Parkhurst

Nathan Wong

Zachary Rae

Michael C Kelly

Stephanie L Goff

Paul F Robbins

Steven A Rosenberg

James C Yang

Affiliations

Soon will be listed here.

Abstract

A common theme across multiple successful immunotherapies for cancer is the recognition of tumor-specific mutations (neoantigens) by T cells. The rapid discovery of such antigen responses could lead to improved therapies through the adoptive transfer of T cells engineered to express neoantigen-reactive T cell receptors (TCRs). Here, through CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing) and TCR-seq of non-small cell lung cancer (NSCLC) tumor-infiltrating lymphocytes (TILs), we develop a neoantigen-reactive T cell signature based on clonotype frequency and CD39 protein and CXCL13 mRNA expression. Screening of TCRs selected by the signature allows us to identify neoantigen-reactive TCRs with a success rate of 45% for CD8 and 66% for CD4 T cells. Because of the small number of samples analyzed (4 patients), generalizability remains to be tested. However, this approach can enable the quick identification of neoantigen-reactive TCRs and expedite the engineering of personalized neoantigen-reactive T cells for therapy.

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