Frontiers in Immunology (Oct 2024)

Transcriptomics profiling of the non-small cell lung cancer microenvironment across disease stages reveals dual immune cell-type behaviors

  • Marcelo Hurtado,
  • Leila Khajavi,
  • Abdelmounim Essabbar,
  • Michael Kammer,
  • Michael Kammer,
  • Ting Xie,
  • Alexis Coullomb,
  • Anne Pradines,
  • Anne Pradines,
  • Anne Casanova,
  • Anne Casanova,
  • Anna Kruczynski,
  • Sandrine Gouin,
  • Estelle Clermont,
  • Estelle Clermont,
  • Léa Boutillet,
  • Maria Fernanda Senosain,
  • Maria Fernanda Senosain,
  • Yong Zou,
  • Yong Zou,
  • Shillin Zhao,
  • Prosper Burq,
  • Abderrahim Mahfoudi,
  • Jerome Besse,
  • Pierre Launay,
  • Alexandre Passioukov,
  • Eric Chetaille,
  • Gilles Favre,
  • Fabien Maldonado,
  • Francisco Cruzalegui,
  • Olivier Delfour,
  • Julien Mazières,
  • Julien Mazières,
  • Vera Pancaldi,
  • Vera Pancaldi

DOI
https://doi.org/10.3389/fimmu.2024.1394965
Journal volume & issue
Vol. 15

Abstract

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BackgroundLung cancer is the leading cause of cancer death worldwide, with poor survival despite recent therapeutic advances. A better understanding of the complexity of the tumor microenvironment is needed to improve patients’ outcome.MethodsWe applied a computational immunology approach (involving immune cell proportion estimation by deconvolution, transcription factor activity inference, pathways and immune scores estimations) in order to characterize bulk transcriptomics of 62 primary lung adenocarcinoma (LUAD) samples from patients across disease stages. Focusing specifically on early stage samples, we validated our findings using an independent LUAD cohort with 70 bulk RNAseq and 15 scRNAseq datasets and on TCGA datasets.ResultsThrough our methodology and feature integration pipeline, we identified groups of immune cells related to disease stage as well as potential immune response or evasion and survival. More specifically, we reported a duality in the behavior of immune cells, notably natural killer (NK) cells, which was shown to be associated with survival and could be relevant for immune response or evasion. These distinct NK cell populations were further characterized using scRNAseq data, showing potential differences in their cytotoxic activity.ConclusionThe dual profile of several immune cells, most notably T-cell populations, have been discussed in the context of diseases such as cancer. Here, we report the duality of NK cells which should be taken into account in conjunction with other immune cell populations and behaviors in predicting prognosis, immune response or evasion.

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