Immune Profiling of Cancer Patients Treated with Immunotherapy: Advances and Challenges

Abstract

The recent advances in immunotherapy and the availability of novel drugs to target the tumor microenvironment have dramatically changed the paradigm of cancer treatment. Nevertheless, a significant proportion of cancer patients are unresponsive or develop resistance to these treatments. With the aim to increase the clinical efficacy of immunotherapy, combinations of agents and standard therapies with complementary actions have been developed mostly on an empirical base, since their mechanisms of actions are not yet fully dissected. The characterization of immune responsiveness and its monitoring along with the treatment of cancer patients with immunotherapy can provide insights into the mechanisms of action of these therapeutic regimens and contribute to the optimization of patients' stratification and of combination strategies and to the prediction of treatment-related toxicities. Thus far, none of the immunomonitoring strategies has been validated for routine clinical practice. Moreover, it is becoming clear that the genomic and molecular make-up of tumors and of the infiltrating immune system represent important determinants of the clinical responses to immunotherapy. This review provides an overview of different approaches for the immune profiling of cancer patients and discusses their advantages and limitations. Recent advances in genomic-based assays and in the identification of host genomic relationships with immune responses represent promising approaches to identify molecular determinants and biomarkers to improve the clinical efficacy of cancer immunotherapy.

Keywords: T cell responses; genomic determinants; immune monitoring; immunotherapy; soluble markers.

Figure 1

Immune profiling of cancer patients. 1. Tumor and immune cells in tissues specimens can be evaluated through IHC or mass cytometry for: i. defined marker expressions, assessment of type, quantity, and localization of immune infiltration, spatial relationship between tumor and immune cells. ii. Molecular analysis of gene signatures. iii. Genomic and epigenetic analyses. Ideally, a longitudinal analysis of tumor tissues should be performed to monitor changes along with treatment regimens. 2. Peripheral blood represents a minimally invasive procedures to monitor dynamic changes of immune responses through: iv. Immunophenotypic characterization of subpopulations of lymphocytes and monocyte/myeloid cells. v. Monitoring antigen-specific T cell responses or humoral responses. vi. Assessment of soluble biomarkers. vii. Genomic profiling of blood cells. viii. Transcriptomic analyses. 3. Host microbiome can shape the immune responses and affect patients’ clinical outcome after immunotherapy. The assessment of microbiome genomics is assuming a relevant role in immune monitoring of cancer patients. IHC: immunohistochemistry; WGS: whole-genome sequencing; WES: whole-exome sequencing; RNAseq: sequencing of RNA; TCR seq: sequencing of T cell receptor; miRNAs: microRNAs; MDSCs: myeloid-derived suppressor cells; ELISA: enzyme-linked immunosorbent assay; EliSpot: enzyme-linked immunospot assay; miRNAs: micro RNAs.