Role of immunotherapy in gastro‐enteropancreatic neuroendocrine neoplasms (gep‐nens): Current advances and future directions

Abstract

The role of the immune system in cancer treatment was first described in the late 19th Century when Dr William Coley observed that injecting killed bacteria into sarcoma led to tumour shrinkage. 1-5 In the past few decades, significant advances have been made in the understanding of the intersection between immune surveillance and tumour growth. It is because of this that immune-mediated therapeutic advances have occurred more recently. The gastroenteropancreatic (GEP)-neuroendocrine neoplasms (NEN) tumour microenvironment is enriched with immune cells that include natural killer cells, immunosuppressive regulatory T cells, tumour-infiltrating lymphocytes (TILs) and tumour-associated macrophages. From this, various therapeutic approaches are being studied to unleash the immune system and control the growth of NENs. 6 One approach in particular uses check point inhibitors of the programmed cell

Efficacy of Immune Checkpoint Inhibitors against Advanced or Metastatic Neuroendocrine Neoplasms: A Systematic Review and Meta-Analysis

“…Three of our included studies evaluated the efficacy of nivolumab plus ipilimumab [35,36,39] and consistently observed a high ORR of 24.1-27.3%. There is now growing evidence that ICI monotherapy has limited effectiveness against NENs, particularly PD tumors [59][60][61], which is consistent with our observations. Only the nivolumab plus ipilimumab combination ICI regimen was evaluable in our study, however, and exploration of the synergistic effect of various combinations of ICIs versus other immunotherapeutic and different anticancer treatments is required.…”

Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin

“…The differences observed in the efficacy and activity of immunotherapy between low- and high-grade NENs across trials may rely on the higher PD-L1 expression, TMB, and enhanced neoantigen presentation, which has been positively correlated to tumour grade 25 . Tumour PD-L1 expression has been associated with ICI efficacy across tumour types and positively associated with poorer survival in NENs 26 .…”

Immune Checkpoint Blockade in Lung Carcinoids with Aggressive Behaviour: One More Arrow in Our Quiver?

“…Importantly, the results of both prospective trials and case studies suggest that checkpoint blockade might exert a higher antitumor activity in patients with LCs than with low-grade WD GEP-NENs [26,53,54]. However, it is important to highlight that available evidence on the efficacy of ICIs in advanced LCs mainly applies to ACs, with TCs requiring even further investigation.…”