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In the treatment of advanced non-small cell lung cancer (NSCLC), immune checkpoint inhibitors have shown remarkable results. However, not all patients with NSCLC respond to this drug treatment or receive durable benefits. Thus, patient stratification and selection, as well as the identification of predictive biomarkers, represent pivotal aspects to address. In this framework, metabolomics can be used to support the discrimination between responders and non-responders. Here, metabolomics was used to analyze the sera samples from 50 patients with NSCL treated with immune checkpoint inhibitors. All the samples were collected before the beginning of the treatment and were analyzed by NMR spectroscopy and multivariate statistical analyses. Significantly, we show that the metabolomic fingerprint of serum acts as a predictive “collective” biomarker to immune checkpoint inhibitors response, being able to predict individual therapy outcome with > 80% accuracy. Metabolomics represents a potential strategy for the real-time selection and monitoring of patients treated with immunotherapy. The prospective identification of responders and non-responders could improve NSCLC treatment and patient stratification, thus avoiding ineffective therapeutic strategies.

Parathyroid hormone-related protein (PTH-rP), a protein produced by prostate carcinoma and other epithelial cancers, is a key agent in the development of bone metastases. We investigated whether the protein follows the self-tolerance paradigm or can be used as a target Ag for anticancer immunotherapy by investigating the immunogenicity of two HLA-A(*)02.01-binding PTH-rP-derived peptides (PTR-2 and -4) with different affinity qualities. PTH-rP peptide-specific CTL lines were generated from the PBMC of two HLA-A(*)02.01+ healthy individuals, stimulated in vitro with PTH-rP peptide-loaded autologous dendritic cells and IL-2. The peptide-specific CTLs were able to kill PTH-rP+HLA-A(*)02.01+ breast and prostate carcinoma cell lines. The two peptides were also able to elicit a strong antitumor PTH-rP-specific CTL response in HLA-A(*)02.01 (HHD) transgenic mice. The vaccinated mice did not show any sign of side effects due to cell-mediated autoimmunity or toxicity. In this study we describe two immunogenic and toxic-free PTH-rP peptides as valid candidates for the design of peptide-based vaccination strategies against prostate cancer and bone metastases from the most common epithelial malignancies.

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