Current status of immunotherapy in gastrointestinal malignancies

Abstract

Gastrointestinal (GI) malignant neoplasms have a high global incidence and a huge impact on cancer-associated mortality. In the past years, excitement was growing among oncologists and patients alike for the use of immunotherapy, specifically immune checkpoint inhibitors. The approval of several PD-1/PD-L1 and CTLA-4 inhibitors radically changed the treatment landscape in many cancer types and established immune-oncology as a new treatment strategy against cancer. Despite major breakthrough reports, shortcomings of immune checkpoint inhibitors (ICI) have been observed, including primary and acquired treatment resistance, especially in patients receiving ICIs as a single treatment. Several immunotherapies for the treatment of GI tumors have recently emerged; however, checkpoint inhibition has not yet shown similar success in GI malignancies compared to other solid tumors. Various phase I–III trials focusing on immunotherapies for GI tumors have found only moderate to unsatisfactory objective response rates (ORR), ranging between 10 % and 25 %. In particular, negative studies have been reported in gastric and pancreatic cancer. Nevertheless, small subsets of cancers, such as DNA mismatch repair deficient (dMMR)/microsatellite instable (MSI) cancers, among others, seem to benefit from treatment with immune checkpoint inhibition. Routine testing for the rare molecular features that can predict response should be implemented in clinical routine for all GI tumors, and large scale clinical trials to identify predictive biomarkers are needed. This article will address the current use and evidence for immunotherapy in GI malignancies and future trends in this area for clinical practice.

PD-L1 – inhibitors in neuroendocrine neoplasia

“…The recent introduction of immune checkpoint inhibitors has changed treatment algorithms for many patients, including many types of gastrointestinal cancers. [ 9 ] PD-1/PD-L1 is the best studied immune check-point in the context of cancer. [ 10 ] PD-1 represents an inhibitory receptor, which is found on different immune cells including T- and B-cells as well as natural killer cells.…”

Mining the TCGA Database for Microenvironment‐Related Genes with Prognostic Value in Gastric Cancer

“…However, ICIs have shown limited survival bene ts to GC patients. Most patients with GC either do not respond to ICIs, develop primary and acquired treatment resistance [21], or experience immune-related adverse events [22].…”

Circulating levels of microRNA193a-5p predict outcome in early stage hepatocellular carcinoma

“…Thus, we cannot answer the important question whether an HCC patient with an initial serum level above our ideal prognostic cut-off value might have had a similar or even better outcome if treated differently. Given the ongoing studies on adjuvant immunotherapies after resection of HCC [ 29 ], a biomarker identifying patients that should receive additional therapy after surgery could be of valuable clinical relevance. Finally, we concentrated on the patients’ OS as a primary endpoint only.…”