Structural pathways of cytokines may illuminate their roles in regulation of cancer development and immunotherapy

Emine Guven-Maiorov, Saliha Ece Acuner-Ozbabacan, Ozlem Keskin, Attila Gursoy, Ruth Nussinov*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


Cytokines are messengers between tissues and the immune system. They play essential roles in cancer initiation, promotion, metastasis, and immunotherapy. Structural pathways of cytokine signaling which contain their interactions can help understand their action in the tumor microenvironment. Here, our aim is to provide an overview of the role of cytokines in tumor development from a structural perspective. Atomic details of protein-protein interactions can help in understanding how an upstream signal is transduced; how higher-order oligomerization modes of proteins can influence their function; how mutations, inhibitors or antagonists can change cellular consequences; why the same protein can lead to distinct outcomes, and which alternative parallel pathways can take over. They also help to design drugs/inhibitors against proteins de novo or by mimicking natural antagonists as in the case of interferon-γ. Since the structural database (PDB) is limited, structural pathways are largely built from a series of predicted binary protein-protein interactions. Below, to illustrate how protein-protein interactions can help illuminate roles played by cytokines, we model some cytokine interaction complexes exploiting a powerful algorithm (PRotein Interactions by Structural Matching-PRISM).

Original languageEnglish
Pages (from-to)663-683
Number of pages21
Issue number2
StatePublished - Jun 2014


  • Cancer immunotherapy
  • Cytokines
  • Protein interaction prediction
  • Protein interactions
  • Structural pathways
  • Structural pathways of cytokines
  • Structures of cytokines


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