Is there a causal link between PTEN deficient tumors and immunosuppressive tumor microenvironment?

Çetintaş, Vildan Bozok; Batada, Nizar N.

doi:10.1186/s12967-020-02219-w

Cited by 50 publications

(39 citation statements)

References 97 publications

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“…In particular, PTEN expression (or lack thereof) in cancer cells attracts different immune cell populations to the TME; on the other hand, PTEN function in immune cells regulates their activation status [8]. As schematically depicted in Figure 1, the overall effect of PTEN loss of function in different cellular compartments shifts the balance towards an immunosuppressive TME [47][48][49]. Here, we give a comprehensive overview of the potential role of PTEN in the regulation of the immunosuppressive aspects of the TME (Figure 1).…”

Section: Pten In Immunoevasionmentioning

confidence: 99%

PTEN Function at the Interface between Cancer and Tumor Microenvironment: Implications for Response to Immunotherapy

Cognetti

Bazzichetto

Falcone

et al. 2020

IJMS

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Mounting preclinical and clinical evidence indicates that rewiring the host immune system in favor of an antitumor microenvironment achieves remarkable clinical efficacy in the treatment of many hematological and solid cancer patients. Nevertheless, despite the promising development of many new and interesting therapeutic strategies, many of these still fail from a clinical point of view, probably due to the lack of prognostic and predictive biomarkers. In that respect, several data shed new light on the role of the tumor suppressor phosphatase and tensin homolog on chromosome 10 (PTEN) in affecting the composition and function of the tumor microenvironment (TME) as well as resistance/sensitivity to immunotherapy. In this review, we summarize current knowledge on PTEN functions in different TME compartments (immune and stromal cells) and how they can modulate sensitivity/resistance to different immunological manipulations and ultimately influence clinical response to cancer immunotherapy.

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Section: Pten In Immunoevasionmentioning

confidence: 99%

PTEN Function at the Interface between Cancer and Tumor Microenvironment: Implications for Response to Immunotherapy

Cognetti

Bazzichetto

Falcone

et al. 2020

IJMS

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“…Furthermore, V158F has been predicted to lead to PTEN inactivation. In patients with HER-2-positive GC, PTEN deletion mutations are associated with Trastuzumab resistance, and the loss of heterozygosis of this gene has been reported more frequently in GC [42]. The relationship between PTEN protein deletion and various gene alterations in GC is not clear.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological features of Epstein-Barr virus infection, microsatellite instability, tumor mutation burden and PD-L1 status in Chinese patients with gastric cancer

Zhang

Li³

2020

Preprint

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Objectives: Gastric cancer (GC) is the 4th most common type of cancer worldwide. Different GC subtypes exhibit unique molecular features that may potentially guide therapeutic decisions. The aim of the present study was to investigate Epstein-Barr virus (EBV) infection, microsatellite instability (MSI) status, the expression of programmed death-ligand 1 (PD-L1) and gene mutations in patients with surgically-treated GC. Methods: The data of 2,504 GC patients, who underwent potentially curative gastrectomy with lymphadenectomy at Peking University Cancer Hospital between 2013 and 2018, were reviewed from a prospectively collected medical database. We also analyzed the clinicopathological factors associated with the immunohistochemistry (IHC) profiles of these patients, and genetic alterations were analyzed using next generation sequencing (NGS). Results: Mismatch repair-deficient (d-MMR) GC patients were found to have a higher probability of expressing PD-L1 (p<0.001, PD-L1 cutoff value = 1%). In addition, 4 and 6.9% of the 2,504 gastric cancer patients were EBV-positive and d-MMR, respectively. The number of MLH1/PMS2-negative cases was 126 (6%), and the number of MSH2/MSH6-negative cases was 14 (0.9%). d-MMR status was associated with a diffuse/mixed group (p<0.05), but not with tumor differentiation. Furthermore, MSI and d-MMR GC status (detected by NGS and IHC, respectively) were consistently high, and the rate of MSI was higher in patients with d-MMR GC. A number of genes associated with DNA damage repair were detected in GC patients with MSI, including POLE, ETV6, BRCA and RNF43. In patients with a high tumor mutation burden, the most significantly mutated genes were LRP1B (79.07%), ARID1A (74.42%), RNF43 (69.77%), ZFHX3 (65.12%), TP53 (58.14%), GANS (51.16%), BRCA2 (51.16%), PIK3CA (51.16%), NOTCH1 (51.16%), SMARCA4 (48.84%), ATR (46.51%), POLE (41.86%) and ATM (39.53%). Conclusions: Using IHC and NGS, MSI status, protein expression, TMB and genetic alterations were identified in patients with GC, which provides a theoretical basis for the future clinical treatment of GC.

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“…It is predicted that V158fs will lead to the inactivation of PTEN. In HER-2 positive GC patients, PTEN deletion mutations are associated with Trastuzumab resistance, and the loss of heterozygosis of this gene has been reported more frequently in gastric cancer [31]. In solid tumor patients receiving immunotherapy, the median OS of patients with POLE/POLD1 mutation was signi cantly better than that of non-carriers.…”

Section: Discussionmentioning

confidence: 99%

Clinic-pathological Features of Epstein-barr Virus Infection, Microsatellite Instability, Tumor Mutation Burden and PD-L1 Status in 2504 Chinese Gastric Cancer Patients

Zhang

2020

Preprint

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Objectives: Gastric cancer is the 4th most common cancer worldwide. Different subtype showed unique molecular features that could potentially guide therapeutic decisions. The aim of this study was to investigate the Epstein-Barr virus infection, microsatellite instability status, PD-L1 expression and gene mutation in surgically treated gastric cancer patients. Methods: We reviewed all GC patients who underwent potentially curative gastroectomy with lymphadenectomy at Peking University Cancer Hospital between 2013 and 2018 from a prospective collected medical database. We analyzed the clinic-pathological factors associated with immunohistochemistry profiles. We also analyzed gene changes through next-generation sequencing. Results: d-MMR gastric cancer patients are more likely to expression programmed death-ligand 1 (p<0.001, programmed death-ligand 1 cut off value 1%). EBV-positive and d-MMR patients were identified in 4% and 7.5% of the 2504 gastric cancer patients, respectively. The MLH1/PMS2 negative case number was 126. The MSH2/MSH6 negative case number was 14. d-MMR status was related to diffuse/mixed group (p<0.05), but not related to tumor differentiation. In our study, the microsatellite instability results detected by next generation sequencing and d-MMR gastric cancer results detected by immunohistochemistry were in high consistency. d-MMR gastric cancer patients had more microsatellite instability core. Many pathogenic genes were detected in microsatellite instability gastric cancer patients, such as POLE, ETV6, TP53, BRCA, RNF43 and other genes. Conclusion: Through immunohistochemistry and next generation sequencing, we got MSI status, protein expression, TMB and gene changes of GC, which provided a theoretical basis for future G clinical treatment.

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Is there a causal link between PTEN deficient tumors and immunosuppressive tumor microenvironment?

Cited by 50 publications

References 97 publications

PTEN Function at the Interface between Cancer and Tumor Microenvironment: Implications for Response to Immunotherapy

PTEN Function at the Interface between Cancer and Tumor Microenvironment: Implications for Response to Immunotherapy

Clinicopathological features of Epstein-Barr virus infection, microsatellite instability, tumor mutation burden and PD-L1 status in Chinese patients with gastric cancer

Clinic-pathological Features of Epstein-barr Virus Infection, Microsatellite Instability, Tumor Mutation Burden and PD-L1 Status in 2504 Chinese Gastric Cancer Patients

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