Infiltration of Alternatively Activated Macrophages in Cancer Tissue Is Associated with MDSC and Th2 Polarization in Patients with Esophageal Cancer

Gao, Jingjing; Wu, Yue; Su, Zhaoliang; Barnie, Prince Amoah; Jiao, Zhijun; Bie, Qingli; Lu, Liwei; Wang, Shengjun; Xu, Huaxi

doi:10.1371/journal.pone.0104453

Cited by 48 publications

(53 citation statements)

References 31 publications

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“…Accordingly, human M-MDSCs from head and neck cancer patients were found to exert a suppressive function via ARG1 (49). Elevated IL-13 levels, concomitant with increased MDSC, M2, and/or ARG1 levels, were reported in human gastrointestinal cancers (50,51). Moreover, an ILC2/IL-13/M2 axis was recently reported in mouse models of parasitic infections (52, 53) and of breast cancer (29), supporting our results.…”

Section: Discussionsupporting

confidence: 88%

ILC2-modulated T cell–to-MDSC balance is associated with bladder cancer recurrence

Chevalier

Trabanelli

Racle

et al. 2017

Journal of Clinical Investigation

184

151

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Section: Discussionsupporting

confidence: 88%

ILC2-modulated T cell–to-MDSC balance is associated with bladder cancer recurrence

Chevalier

Trabanelli

Racle

et al. 2017

Journal of Clinical Investigation

184

151

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“…þ cells) infiltrated to more than half of esophageal tumor tissues (32). Although we did not analyze these inhibitory factors in patients' tumor samples, they might have played a role in tumor responses in this study.…”

Section: Cd163mentioning

confidence: 84%

Adoptive Transfer of MAGE-A4 T-cell Receptor Gene-Transduced Lymphocytes in Patients with Recurrent Esophageal Cancer

Kageyama

Ikeda

Miyahara

et al. 2015

Clinical Cancer Research

146

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Purpose: Preparative lymphodepletion, the temporal ablation of the immune system, has been reported to promote persistence of transferred cells along with increased rates of tumor regression in patients treated with adoptive T-cell therapy. However, it remains unclear whether lymphodepletion is indispensable for immunotherapy with T-cell receptor (TCR) gene-engineered T cells.Experimental Design: We conducted a first-in-man clinical trial of TCR gene-transduced T-cell transfer in patients with recurrent MAGE-A4-expressing esophageal cancer. The patients were given sequential MAGE-A4 peptide vaccinations. The regimen included neither lymphocyte-depleting conditioning nor administration of IL2. Ten patients, divided into 3 dose cohorts, received T-cell transfer.Results: TCR-transduced cells were detected in the peripheral blood for 1 month at levels proportional to the dose administered, and in 5 patients they persisted for more than 5 months. The persisting cells maintained ex vivo antigen-specific tumor reactivity. Despite the long persistence of the transferred T cells, 7 patients exhibited tumor progression within 2 months after the treatment. Three patients who had minimal tumor lesions at baseline survived for more than 27 months.Conclusions: These results suggest that TCR-engineered T cells created by relatively short-duration in vitro culture of polyclonal lymphocytes in peripheral blood retained the capacity to survive in a host. The discordance between T-cell survival and tumor regression suggests that multiple mechanisms underlie the benefits of preparative lymphodepletion in adoptive T-cell therapy.

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“…In macrophages and dendritic cells PD-L2 transcription is regulated by IL4/IL13/STAT6 signaling (41,42), raising the possibility that PD-L2 epithelial expression in EAC and BE may result from IL4/IL13 expression (29,43). The therapeutic role of inhibiting PD-L2 is controversial.…”

Section: Pd-l1 Expression In Gastro-esophageal Tumorsmentioning

confidence: 99%

The promise of PD-1 inhibitors in gastro-esophageal cancers: microsatellite instability vs. PD-L1

Jin

Yoon

2016

J. Gastrointest. Oncol.

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Preliminary clinical studies of anti-programmed cell death-1 (anti-PD-1) therapy in gastroesophageal cancers have suggested promising single-agent activity. In patients who received prior treatment for advanced disease, pembrolizumab has been associated with a response rate of 20% in programmed cell death-1 ligand 1 (PD-L1)-positive tumors, and nivolumab with a response rate of 12% in unselected tumors.Both agents yielded a median duration of response lasting ~6-7 months. PD-L1 expression and microsatellite instability (MSI) have emerged as potential predictive markers for PD-1/PD-L1 blockade. PD-L1 expression in tumor cells and in immune cells within the tumor microenvironment has been detected in 14-24% and ~35% of patients with gastro-esophageal cancer, respectively. PD-L1 tumor cell expression appears to be more common in Epstein-Barr virus (EBV)-positive gastric cancers (GCs) and has been associated with an increased density of tumor-infiltrating lymphocytes (TIL). To date, data are too sparse to determine whether PD-L1 expression predicts efficacy of anti-PD-1 therapy in gastro-esophageal cancer, but data from other tumor types have not been consistent regarding its predictive value. MSI occurs in 10-20% of gastro-esophageal cancers and arises from deficient mismatch repair (MMR). MSI is highly correlated with non-synonymous mutation burden, as well as a dense accumulation of TILs. MSI has been associated with improved response to anti-PD-1 therapy in gastrointestinal cancers. Multiple studies are ongoing which examine therapeutic blockade of the PD-1/PD-L1 axis in unselected patients with gastro-esophageal cancer, as well as patients whose tumors express PD-L1 or exhibit MSI. These studies will clarify their activity in this disease and potentially can determine whether identify a strong predictive biomarker can be identified.Checkpoint inhibition is also being studied in combination with curative-intent chemo (radio) therapy and surgery.Keywords: Programmed cell death-1 (PD-1); programmed cell death-1 ligand 1 (PD-L1); gastro-esophageal cancer; microsatellite instability (MSI)

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Infiltration of Alternatively Activated Macrophages in Cancer Tissue Is Associated with MDSC and Th2 Polarization in Patients with Esophageal Cancer

Cited by 48 publications

References 31 publications

ILC2-modulated T cell–to-MDSC balance is associated with bladder cancer recurrence

ILC2-modulated T cell–to-MDSC balance is associated with bladder cancer recurrence

Adoptive Transfer of MAGE-A4 T-cell Receptor Gene-Transduced Lymphocytes in Patients with Recurrent Esophageal Cancer

The promise of PD-1 inhibitors in gastro-esophageal cancers: microsatellite instability vs. PD-L1

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