New clinical advances in immunotherapy for the treatment of solid tumours

Abstract

SummaryAdvances in understanding the mechanisms of cancer cells for evading the immune system surveillance, including how the immune system modulates the phenotype of tumours, have allowed the development of new therapies that benefit from this complex cellular network to specifically target and destroy cancer cells. Immunotherapy researchers have mainly focused on the discovery of tumour antigens that could confer specificity to immune cells to detect and destroy cancer cells, as well as on the mechanisms leading to an improved activation of effector immune cells. The Food and Drug Administration approval in 2010 of ipilumumab for melanoma treatment and of pembrolizumab in 2014, monoclonal antibodies against T-lymphocyte-associated antigen 4 and programmed cell death 1, respectively, are encouraging examples of how research in this area can successfully translate into clinical use with promising results. Currently, several ongoing clinical trials are in progress testing new anticancer therapies based on the enhancement of immune cell activity against tumour antigens. Here we discuss the general concepts related to immunotherapy and the recent application to the treatment of cancer with positive results that support their consideration of clinical application to patients.

Immune checkpoint inhibitors: a narrative review of considerations for the anaesthesiologist

“…In a similar mechanism to CTLA-4, the PD-1 (CD279) receptor, another structural homologue of the CD28 receptor, blocks T-cell proliferation and induces immunological tolerance. 15 PD-1 (CD279) binds to PD-L1 (CD274) ligand, PD-L2 (CD273) ligand, or both, which belong to the family of B7 proteins ( Fig. 2b).…”

Targeting Transcriptional Regulators of CD8+ T Cell Dysfunction to Boost Anti-Tumor Immunity

“…The promise of eliciting functional anti-tumor immune response for cancer treatment has been developing for decades to result in a recent explosion of clinical triumphs [ 22 ]. Current therapies successfully utilized in the clinic to boost anti-tumor immunity include diverse methods of active and passive immunization [ 23 , 24 ]. Efforts to increase TIL function generally seek to expand the number of functional anti-tumor T cells, or to reduce immunoinhibitory stimuli present in the patient’s tumor environment [ 23 ].…”

“…Co-therapies used to target multiple pathways inhibiting TIL function are being translated from mouse models to the clinic [ 25 , 26 ]. For instance, dual blockade of T cell inhibitory receptors programmed death-1 (PD-1 or CD279) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4 or CD152) has greatly increased progression-free survival and overall response rates of an encouraging fraction of patients bearing previously incurable solid tumors [ 24 , 25 , 26 , 27 , 28 ]. Approximately 50% of patients with advanced melanoma experienced tumor regression, and ongoing clinical trials, show promise in a variety of malignancies.…”

“…Although anti-tumor responses may not clear all tumors, other promising combinatorial immunotherapies are in trials [ 23 ]. Current research is largely focused on predicting which cancer patients will benefit from specific immunotherapies [ 24 , 29 ].…”

Immune reprogramming via PD-1 inhibition enhances early-stage lung cancer survival

“…Non-small-cell lung cancer (NSCLC) constitutes approximately 80% of all lung cancer cases and has a 5-year survival rate of only 15%-20% (3). Immune checkpoint inhibitors have begun to revolutionize the survival prospects of cancer patients (4)(5)(6), particularly those blocking the PD-1/PD-L1 (programmed cell death 1/programmed cell death 1 ligand 1) axis, which have yielded objective response rates of about 20% and are currently approved by the FDA for a subset of patients with advanced disease (7)(8)(9). Importantly, in patients with advanced NSCLC and PD-L1 expression on at least 50% of tumor cells, PD-1 inhibition was associated with longer progression-free and overall survival than platinum-based chemotherapy (10).…”