Immunotherapy Strategies for Gastrointestinal Stromal Tumor

Arshad, Junaid; Costa, Philippos Apolinário; Barreto-Coelho, Priscila; Valdes, Brianna Nicole; Trent, Jonathan C.

doi:10.3390/cancers13143525

Cited by 23 publications

(14 citation statements)

References 35 publications

(81 reference statements)

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“…Moreover, there are also some less abundant immune cells infiltrated in GIST, including natural killer (NK) cells, B lymphocytes, dendritic cells (DCs), natural killer T (NKT) cells, gamma delta (γδ) T cells, neutrophils, eosinophils and mast cells, etc. [42, 94,96,100,101,103,106,[113][114][115]. The intratumoral distribution patterns of immune cells in GIST are variable; they are mainly diffusely distributed around blood vessels with a small amount distributed in aggregates [94,96,100,101,105].…”

Section: Immune Cell Landscape Of Gistmentioning

confidence: 99%

Advances in immunology and immunotherapy for mesenchymal gastrointestinal cancers

Chen

Yang

et al. 2023

Mol Cancer

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Mesenchymal gastrointestinal cancers are represented by the gastrointestinal stromal tumors (GISTs) which occur throughout the whole gastrointestinal tract, and affect human health and economy globally. Curative surgical resections and tyrosine kinase inhibitors (TKIs) are the main managements for localized GISTs and recurrent/metastatic GISTs, respectively. Despite multi-lines of TKIs treatments prolonged the survival time of recurrent/metastatic GISTs by delaying the relapse and metastasis of the tumor, drug resistance developed quickly and inevitably, and became the huge obstacle for stopping disease progression. Immunotherapy, which is typically represented by immune checkpoint inhibitors (ICIs), has achieved great success in several solid tumors by reactivating the host immune system, and been proposed as an alternative choice for GIST treatment. Substantial efforts have been devoted to the research of immunology and immunotherapy for GIST, and great achievements have been made. Generally, the intratumoral immune cell level and the immune-related gene expressions are influenced by metastasis status, anatomical locations, driver gene mutations of the tumor, and modulated by imatinib therapy. Systemic inflammatory biomarkers are regarded as prognostic indicators of GIST and closely associated with its clinicopathological features. The efficacy of immunotherapy strategies for GIST has been widely explored in pre-clinical cell and mouse models and clinical experiments in human, and some patients did benefit from ICIs. This review comprehensively summarizes the up-to-date advancements of immunology, immunotherapy and research models for GIST, and provides new insights and perspectives for future studies.

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Section: Immune Cell Landscape Of Gistmentioning

confidence: 99%

Advances in immunology and immunotherapy for mesenchymal gastrointestinal cancers

Chen

Yang

et al. 2023

Mol Cancer

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“…The role of immunotherapy in GISTs is still unclear, although the mechanisms of immune escape and immune surveillance are known to be well represented in this kind of tumor [ 120 ].…”

Section: Future Perspectives and Ongoing Clinical Trialsmentioning

confidence: 99%

Molecular Tailored Therapeutic Options for Advanced Gastrointestinal Stromal Tumors (GISTs): Current Practice and Future Perspectives

Catalano

Cremante

Dalmasso

et al. 2023

Cancers

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Gastrointestinal stromal tumors (GISTs) are one of the most common mesenchymal tumors characterized by different molecular alterations that lead to specific clinical presentations and behaviors. In the last twenty years, thanks to the discovery of these mutations, several new treatment options have emerged. This review provides an extensive overview of GISTs’ molecular pathways and their respective tailored therapeutic strategies. Furthermore, current treatment strategies under investigation and future perspectives are analyzed and discussed.

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“…Indeed, the development of immunotherapy has provided a host of opportunities to match novel targets with innovative therapeutic strategies in many cancer types, and GISTs have been no exception to the rule [ 13 , 14 , 15 , 16 ]. Clinical studies have been developed to investigate immune checkpoint inhibitors (ICI) activity in GISTs combined with TKI, but none of them managed to show evidence of synergism [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Integrated Antitumor Activities of Cellular Immunotherapy with CIK Lymphocytes and Interferons against KIT/PDGFRA Wild Type GIST

Fiorino

Merlini

D’Ambrosio

et al. 2022

IJMS

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Gastrointestinal stromal tumors (GISTs) are rare, mesenchymal tumors of the gastrointestinal tract, characterized by either KIT or PDGFRA mutation in about 85% of cases. KIT/PDGFRA wild type gastrointestinal stromal tumors (wtGIST) account for the remaining 15% of GIST and represent an unmet medical need: their prevalence and potential medical vulnerabilities are not completely defined, and effective therapeutic strategies are still lacking. In this study we set a patient-derived preclinical model of wtGIST to investigate their phenotypic features, along with their susceptibility to cellular immunotherapy with cytokine-induced killer lymphocytes (CIK) and interferons (IFN). We generated 11 wtGIST primary cell lines (wtGISTc). The main CIK ligands (MIC A/B; ULBPs), along with PD-L1/2, were expressed by wtGISTc and the expression of HLA-I molecules was preserved. Patient-derived CIK were capable of intense killing in vitro against wtGISTc resistant to both imatinib and sunitinib. We found that CIK produce a high level of granzyme B, IFNα and IFNγ. CIK-conditioned supernatant was responsible for part of the observed tumoricidal effect, along with positive bystander modulatory activities enhancing the expression of PD-L1/2 and HLA-I molecules. IFNα, but not In, had direct antitumor effects on 50% (4/8) of TKI-resistant wtGISTc, positively correlated with the tumor expression of IFN receptors. wtGIST cells that survived IFNα were still sensitive to CIK immunotherapy. Our data support the exploration of CIK immunotherapy in clinical studies for TKI-resistant wtGIST, proposing reevaluation for IFNα within this challenging setting.

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Immunotherapy Strategies for Gastrointestinal Stromal Tumor

Cited by 23 publications

References 35 publications

Advances in immunology and immunotherapy for mesenchymal gastrointestinal cancers

Advances in immunology and immunotherapy for mesenchymal gastrointestinal cancers

Molecular Tailored Therapeutic Options for Advanced Gastrointestinal Stromal Tumors (GISTs): Current Practice and Future Perspectives

Integrated Antitumor Activities of Cellular Immunotherapy with CIK Lymphocytes and Interferons against KIT/PDGFRA Wild Type GIST

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