Clinical Development of PD-1/PD-L1 Immunotherapy for Gastrointestinal Cancers: Facts and Hopes

Abstract

Gastrointestinal (GI) cancers are among the most deadly malignancies. Although serial incremental survival benefits have been made with cytotoxic chemotherapy with metastatic disease, a plateau of achievement has been reached. Applying modern integrative genomic technology, distinct molecular subgroups have been identified in GI cancers. This not only highlighted the heterogeneity in tumors of each primary anatomical site but also identified novel therapeutic targets in distinct molecular subgroups and might improve the yield of clinical success. Molecular characteristics of tumors and their interaction with the tumor microenvironment would further affect development of combination therapy, including immunotherapy. Currently, immune checkpoint blockade attracts the most intense research, and the successful integration of these novel agents in GI cancers in the treatment paradigm requires an in-depth understanding of the diverse immune environment of these cancers. .

The evolving immunotherapeutic landscape in advanced oesophagogastric cancer

“…This prognostic difference between the TCGA and ACRG may be related to the limited follow up of the TCGA, the incorporation of clinical characteristics into the ACRG system and the inclusion of molecular aberrations in the ACRG system which are not mutually exclusive if applied within the TCGA system. 27 The TCGA also recently reported the genomic characterisation of oesophageal adeno and squamous carcinomas. 28 Other molecular categorisations of relevance include one which attempts to link the alterations to markers of potential therapeutic significance.…”

Introducing a New Series: Immunotherapy Facts and Hopes

“…To commission and guide this series of reviews, we followed two rules: (i) identify authors who would authoritatively cover the field from a translational perspective, (ii) invite each review focused around areas of major progress in a particular disease. The collection commenced publication in 2017 and will be ongoing as new developments are established (3)(4)(5)(6)(7)(8).…”

“…Clínica Universidad de Navarra and CIMA, Pamplona, Spain 2. CIBERONC, Madrid, Spain 3. Yale University School of Medicine, New Haven, Connecticut 4.…”

In tumor cells, thyroid hormone analogues non-immunologically regulate PD-L1 and PD-1 accumulation that is anti-apoptotic

“…PD-L1 production by tumor cells is a natural defense of cancer cells against host immune system destruction, downregulating the antitumor activity of immune T (killer) cells [ 1 , 6 - 8 ]. Antibodies to PD-L1 and to PD-1 have been shown clinically to have important utility in the management of a variety of malignancies [ 9 - 15 ].…”