An activation to memory differentiation trajectory of tumor-infiltrating lymphocytes informs metastatic melanoma outcomes

Abhinav Jaiswal, Akanksha Verma, Ruth Dannenfelser, Marit Melssen, Itay Tirosh, Benjamin Izar, Tae Gyun Kim, Christopher J. Nirschl, K. Sanjana P. Devi, Walter C. Olson, Craig L. Slingluff, Victor H. Engelhard, Levi Garraway, Aviv Regev, Kira Minkis, Charles H. Yoon, Olga Troyanskaya, Olivier Elemento, Mayte Suárez-Fariñas, Niroshana Anandasabapathy

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

There is a need for better classification and understanding of tumor-infiltrating lymphocytes (TILs). Here, we applied advanced functional genomics to interrogate 9,000 human tumors and multiple single-cell sequencing sets using benchmarked T cell states, comprehensive T cell differentiation trajectories, human and mouse vaccine responses, and other human TILs. Compared with other T cell states, enrichment of T memory/resident memory programs was observed across solid tumors. Trajectory analysis of single-cell melanoma CD8+ TILs also identified a high fraction of memory/resident memory-scoring TILs in anti-PD-1 responders, which expanded post therapy. In contrast, TILs scoring highly for early T cell activation, but not exhaustion, associated with non-response. Late/persistent, but not early activation signatures, prognosticate melanoma survival, and co-express with dendritic cell and IFN-γ response programs. These data identify an activation-like state associated to poor response and suggest successful memory conversion, above resuscitation of exhaustion, is an under-appreciated aspect of successful anti-tumoral immunity.

Original languageEnglish (US)
Pages (from-to)524-544.e5
JournalCancer Cell
Volume40
Issue number5
DOIs
StatePublished - May 9 2022

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Keywords

  • ICB
  • T cell memory
  • TILs
  • immune checkpoint blockade
  • immune persistence
  • melanoma
  • survival
  • systems biology
  • tumor-infiltrating lymphocytes

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