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

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.

Pre-existing inflammatory immune microenvironment predicts the clinical response of vulvar high-grade squamous intraepithelial lesions to therapeutic HPV16 vaccination

“…The combination of multiple biomarkers is likely to increase the sensitivity of the prediction tool. 41 Furthermore, our data strongly suggest that the efficacy of therapeutic vaccines in this patient group can be increased when it is combined with other drugs that induce local acute inflammation, to support the infiltration of vaccine-activated T cells and inflammatory myeloid cells. Hence, our findings show that the current paradigm of personalized cancer immunotherapy also applies to therapeutic vaccines for the treatment of patients with virally induced lesions as well as provides a foundation for future combination therapy studies.…”

Excision Repair Cross Complementation Group 1 Single Nucleotide Polymorphisms and Nivolumab in Advanced Non-Small Cell Lung Cancer

“…PD-L1 expression on tumor cells evaluated by immunohistochemistry (IHC) was the first identified as a potential indicator of benefit and a “logical” biomarker for the prediction of response to PD-1/PD-L1 ICB in lung cancer. Furhter, PD-L1 was largely investigated in a variety of neoplastic diseases with conflicting results ( 36 ).…”

Association of Steroids Use with Survival in Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis

“…The anti-Programmed Death Ligand 1 (PDL-1) durvalumab is the gold standard in unresectable locally advanced PDL-1 positive (tumor proportion score > 1%) Non-Small Cell Lung Cancer (NSCLC) as maintenance treatment after definitive chemoradiotherapy. In advanced NSCLC without EGFR or ALK aberrations, immunotherapy alone is the standard treatment in second line and, in PDL-1 strong positive (tumor proportion score > 50%) tumors, in first line [1]. The combination of chemotherapy plus immunotherapy is a new option in first line in advanced NSCLC, regardless of PDL-1 expression [2][3][4].…”