Human Programmed Cell Death 1 (PD-1): bioinformatic study of the protein and evaluation of therapeutic efficacy in combination with immunotherapy.

Abstract

INTRODUCTION

To function properly, immune system cells (especially T lymphocytes) require activation and deactivation systems (so-called “checkpoints”) that regulate their activity.

Tumors are able to exploit the aforementioned systems to their advantage, while immunological drugs act by interfering with this mechanism.

We will study the hPD-1 protein in depth from a bioinformatics perspective, building a model of the tertiary structure of the protein associated with its ligand hPDL-1; the protein structure will be compared with the structure of the monoclonal antibody Nivolumab, which inhibits the complex.

MATERIALS AND METHODS

For the bioinformatic characterization of the PD1 proteins, its ligand PDL1, and the inhibitory antibody to PD1, algorithms and programs such as Jpred and TMHMM were used to predict the secondary structure of the protein and transmembrane helices, while STRING was used to predict the interaction processes with other molecules.

The program used to perform the structural overlap between the PD1 and PDL1 proteins was Jmol. Meta-analyses performed with AI software (IPDfromKM method) were used to provide an overview of NSCLC.

RESULTS

With Protein Data Bank, we can observe the three-dimensional structures of proteins. With JPred, we can identify the alpha-helices and beta-sheets present in the protein, while with TMHMM, the transmembrane helices.

Comparison of protein structures with Jmol allows us to highlight the presence of deletions and insertions. Images from meta-analyses with IPDfromKM show a significant reduction in the risk of death for all patients treated with a combination of immunotherapy and chemotherapy.

CONCLUSIONS

This study will provide useful tools to predict the functions and behaviors of molecules similar to those studied, as evidenced by Overall Survival studies applied to chemo-immunotherapy combinations.