The Immune Microenvironment of Human Tumors: General Significance and Clinical Impact

Fridman, Wolf-Herman; Dieu-Nosjean, Marie-Caroline; Pagès, Franck; Cremer, Isabelle; Damotte, Diane; Sautès-Fridman, Catheriné; Galon, Jérôme

doi:10.1007/s12307-012-0124-9

Cited by 111 publications

(93 citation statements)

References 59 publications

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“…The presence of tumor infiltrating lymphocytes (TILs) has been associated with an improved prognosis for a number of different tumor types, including colorectal and GCs (19,20). CTL function is closely regulated by the tumor microenvironment, which consists of cancer cells, inflammatory cells, stromal cells and cytokines (21).…”

Section: Pd-1/pd-l1 Pathwaymentioning

confidence: 99%

“…It has been observed that frameshiftinduced neopeptides in patients with MSI-high colorectal cancer are effectively recognized by the immune system. The better outcome of these patients is partly related to the high infiltration of activated CD8+ cytotoxic lymphocytes (CTL) and T helper 1 cells (Th1) (19,(100)(101)(102).…”

Section: Mismatch Repair (Mmr) Deficiency and Hypermutation In Gastromentioning

confidence: 99%

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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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Section: Pd-1/pd-l1 Pathwaymentioning

confidence: 99%

Section: Mismatch Repair (Mmr) Deficiency and Hypermutation In Gastromentioning

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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“…Interestingly, FOXP3+ T-Reg infiltration into tumour core appears higher in immunosuppressed solid organ transplant recipients and is associated with a worse prognosis -an effect not seen in other cancers 18,19,24,26 .…”

Section: Inflammatory Infiltration Of Cancermentioning

confidence: 95%

“…Dendritic cells monitor for tumour antigens that are later presented via lymph drainage, to T and B lymphocytes 19 .…”

Section: Inflammatory Infiltration Of Cancermentioning

confidence: 99%

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The chemokine microenvironment of Squamous Cell Carcinoma and its precursor lesions

Lewandowski¹

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Chemokines play a significant role in attracting immune cells to extravasate to areas of peak expression in response to various stimuli. IL-8, MIP-1α and MIP-1β are known to be highly expressed in multiple cancers, as well as benign skin conditions. Their role in cutaneous Squamous Cell Carcinoma has yet to be established. 67 lesions suspicious for keratinocytic malignancy were sampled from 37 patients and tested for chemokine expression via Flow Cytometry. Each lesion was measured for thickness, histopathological grading, and immune cell infiltration score. Expression of the chemokines IL-8 and MIP-1α

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Tumor-Promoting/Associated Inflammation and the Microenvironment: A State of the Science and New Horizons

Bisson

Amedei

Memeo³

et al. 2017

Translational Toxicology and Therapeutics: Windows of Developmental Susceptibility in Reproduction and Cancer

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The Immune Microenvironment of Human Tumors: General Significance and Clinical Impact

Cited by 111 publications

References 59 publications

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

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

The chemokine microenvironment of Squamous Cell Carcinoma and its precursor lesions

Tumor-Promoting/Associated Inflammation and the Microenvironment: A State of the Science and New Horizons

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