Personalized cancer immunotherapy using Systems Medicine approaches

Abstract

The immune system is by definition multi-scale because it involves biochemical networks that regulate cell fates across cell boundaries, but also because immune cells communicate with each other by direct contact or through the secretion of local or systemic signals. Furthermore, tumor and immune cells communicate, and this interaction is affected by the tumor microenvironment. Altogether, the tumor-immunity interaction is a complex multi-scale biological system whose analysis requires a systemic view to succeed in developing efficient immunotherapies for cancer and immune-related diseases. In this review we discuss the necessity and the structure of a systems medicine approach for the design of anticancer immunotherapies. We support the idea that the approach must be a combination of algorithms and methods from bioinformatics and patient-data-driven mathematical models conceived to investigate the role of clinical interventions in the tumor-immunity interaction. For each step of the integrative approach proposed, we review the advancement with respect to the computational tools and methods available, but also successful case studies. We particularized our idea for the case of identifying novel tumor-associated antigens and therapeutic targets by integration of patient's immune and tumor profiling in case of aggressive melanoma.

Multifaceted Immunomodulatory Nanoliposomes: Reshaping Tumors into Vaccines for Enhanced Cancer Immunotherapy

“…Especially, the combination of tumosomes‐based cancer vaccine with immune‐checkpoint inhibitors that can prevent the attenuation of activated T cells by tumosomes can be a promising platform to improve antitumor immunity in immunosuppressive tumor microenvironments . Fifth, tumosome‐based image‐guided cancer immunotherapy strategies will provide a paradigm shift to personalized medicine because autologous tumor cells may be obtained from the patient and tailored to enhance the therapeutic efficacy . In the future research, we will evaluate the immunological activity of the tumosome after injection into mice through various administration routes (subcutaneous, intramuscular, and intravenous injection).…”

Computational genomics tools for dissecting tumour–immune cell interactions

“…Owing to the limited number of 3D structures of pMHC complexes, modelling or simulation by protein threading and docking methods has to be used. Here, we focus on sequence-based methods, as there are large data sets for training and validation, and they are more suited for screening high-throughput data sets 70 . Early sequence-based methods, such as BIMAS 71 and SYFPEITHI 72 , relied on position-specific scoring matrices (PSSMs), which were defined from experimentally confirmed peptide binders of a particular MHC allele.…”

Precision medicine driven by cancer systems biology

“…Further, neoantigens present themselves as targets for personalized vaccines and cell therapies that target patient-specific cancer mutations [74–79]. The identification of neoantigens can be assisted by structure-based prediction or modeling approaches [80]. Predictions of drug responses in melanoma will eventually improve by looking into gene expression signatures associated with immune sensitivity or resistance [81].…”