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From the Current Issue

What We're Reading

A Sampling of Highlights from the Literature

Cancer Immunol Res June 1 2021 9 (6) 599-599;
Research Articles

γδ T Cells in Merkel Cell Carcinomas Have a Proinflammatory Profile Prognostic of Patient Survival

Nicholas A. Gherardin, Kelly Waldeck, Alex Caneborg, Luciano G. Martelotto, Shiva Balachander, Magnus Zethoven, Pasquale M. Petrone, Andrew Pattison, James S. Wilmott, Sergio M. Quiñones-Parra, Fernando Rossello, Atara Posner, Annie Wong, Alison M. Weppler, Kerwin F. Shannon, Angela Hong, Peter M. Ferguson, Valerie Jakrot, Jeanette Raleigh, Athena Hatzimihalis, Paul J. Neeson, Paolo Deleso, Meredith Johnston, Margaret Chua, Juergen C. Becker, Shahneen Sandhu, Grant A. McArthur, Anthony J. Gill, Richard A. Scolyer, Rodney J. Hicks, Dale I. Godfrey and Richard W. Tothill

Cancer Immunol Res June 1 2021 9 (6) 612-623; DOI:10.1158/2326-6066.CIR-20-0817

The data show many Merkel cell carcinomas have prominent γδ T–cell infiltrates. These unconventional T cells recognize MHC-like ligands and have a proinflammatory gene-expression profile that is associated with improved patient survival, suggesting potential prognostic and therapeutic utility.
Research Articles

Transient Depletion of CD4⁺ Cells Induces Remodeling of the TCR Repertoire in Gastrointestinal Cancer

Hiroyasu Aoki, Satoshi Ueha, Shigeyuki Shichino, Haru Ogiwara, Kohei Shitara, Manami Shimomura, Toshihiro Suzuki, Tetsuya Nakatsura, Makiko Yamashita, Shigehisa Kitano, Sakiko Kuroda, Masashi Wakabayashi, Makoto Kurachi, Satoru Ito, Toshihiko Doi and Kouji Matsushima

Cancer Immunol Res June 1 2021 9 (6) 624-636; DOI:10.1158/2326-6066.CIR-20-0989

Analysis of the blood–tumor overlapping TCR repertoire reveals that transient depletion of CD4⁺ cells causes beneficial remodeling of the TCR repertoire and contributes to the expansion of CD8⁺ tumor-reactive clones in patients with cancer.
Research Articles

Alternative Splicing of the Inhibitory Immune Checkpoint Receptor SLAMF6 Generates a Dominant Positive Form, Boosting T-cell Effector Functions

Emma Hajaj, Elad Zisman, Shay Tzaban, Sharon Merims, Jonathan Cohen, Shiri Klein, Shoshana Frankenburg, Moshe Sade-Feldman, Yuval Tabach, Keren Yizhak, Ami Navon, Polina Stepensky, Nir Hacohen, Tamar Peretz, André Veillette, Rotem Karni, Galit Eisenberg and Michal Lotem

Cancer Immunol Res June 1 2021 9 (6) 637-650; DOI:10.1158/2326-6066.CIR-20-0800

Alternative splicing of SLAMF6 generates two isoforms with opposing effects on T-cell activation; immune checkpoint blockade enriches for the shorter agonistic isoform in T cells, and switching SLAMF6 splicing using antisense oligonucleotides leads to improved antitumor T-cell responses.
Research Articles | AuthorChoice

Chronic Adrenergic Stress Contributes to Metabolic Dysfunction and an Exhausted Phenotype in T Cells in the Tumor Microenvironment

Guanxi Qiao, Minhui Chen, Hemn Mohammadpour, Cameron R. MacDonald, Mark J. Bucsek, Bonnie L. Hylander, Joseph J. Barbi and Elizabeth A. Repasky

Cancer Immunol Res June 1 2021 9 (6) 651-664; DOI:10.1158/2326-6066.CIR-20-0445

T-cell exhaustion impacts immunotherapy efficacy. How T-cell exhaustion is regulated remains incompletely understood. Here, the sympathetic stress response is shown to regulate the development of T-cell exhaustion by modulating CD8⁺ T-cell metabolism and function in the TME.