Patients Selection for Immunotherapy in Solid Tumors: Overcome the Naïve Vision of a Single Biomarker

Diego Signorelli, Patrizia Giannatempo, Giulia Grazia, Marco Maria Aiello, Federica Bertolini, Aurora Mirabile, Sebastiano Buti, Enrico Vasile, Vieri Scotti, Pasquale Pisapia, Maria Silvia Cona, Christian Rolfo, Umberto Malapelle

Research output: Contribution to journalReview articlepeer-review

Abstract

Immunotherapy, and in particular immune-checkpoints blockade therapy (ICB), represents a new pillar in cancer therapy. Antibodies targeting Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) and Programmed Death 1 (PD-1)/Programmed Death Ligand-1 (PD-L1) demonstrated a relevant clinical value in a large number of solid tumors, leading to an improvement of progression free survival and overall survival in comparison to standard chemotherapy. However, across different solid malignancies, the immune-checkpoints inhibitors efficacy is limited to a relative small number of patients and, for this reason, the identification of positive or negative predictive biomarkers represents an urgent need. Despite the expression of PD-L1 was largely investigated in various malignancies, (i.e., melanoma, head and neck malignancies, urothelial and renal carcinoma, metastatic colorectal cancer, and pancreatic cancer) as a biomarker for ICB treatment-patients selection, it showed an important, but still imperfect, role as positive predictor of response only in nonsmall cell lung cancer (NSCLC). Importantly, other tumor and/or microenvironments related characteristics are currently under clinical evaluation, in combination or in substitution of PD-L1 expression. In particular, tumor-infiltrating immune cells, gene expression analysis, mismatch- repair deficiency, and tumor mutational landscape may play a central role in predicting clinical benefits of CTLA-4 and/or PD-1/PD-L1 checkpoint inhibitors. In this review, we will focus on the clinical evaluation of emerging biomarkers and how these may improve the naïve vision of a single- feature patients-based selection.

Original languageEnglish
Article number9056417
JournalBioMed Research International
Volume2019
DOIs
Publication statusPublished - Jan 1 2019

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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