GOLFIG Chemo-Immunotherapy in Metastatic Colorectal Cancer Patients. A Critical Review on a Long-Lasting Follow-Up

Caraglia, Michele; Correale, Pierpaolo; Giannicola, Rocco; Staropoli, Nicoletta; Botta, Cirino; Pastina, Pierpaolo; Nesci, Antonello; Caporlingua, Nadia; Francini, Edoardo; Ridolfi, Laura; Mini, Enrico; Roviello, Giandomenico; Ciliberto, Domenico; Agostino, Rita Maria; Strangio, Alessandra; Azzarello, D.; Nardone, Valerio; Falzea, Antonia Consuelo; Cappabianca, Salvatore; Bocchetti, Marco; D’Arrigo, Graziella; Tripepi, Giovanni; Tassone, Pierfrancesco; Addeo, Raffaele; Giordano, Antonio; Pirtoli, Luigi; Francini, Guido; Tagliaferri, Pierosandro

doi:10.3389/fonc.2019.01102

Cited by 18 publications

(19 citation statements)

References 45 publications

(67 reference statements)

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“…A retrospective clinical study demonstrated that colorectal cancer patients strongly benefited from a combined chemo-immunotherapy regimen (GOLFIG) with respect to progression-free survival and overall survival. In particular, chemotherapeutically pre-treated patients displayed increased anti-tumor responses [ 31 ]. Several recent trials suggest that the antigen load is critical for an efficient treatment response and that immune-modulating treatments, including chemotherapy and RT, could increase the chance to benefit from checkpoint inhibitors and immunotherapy [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Immune Checkpoint Expression on Immune Cells of HNSCC Patients and Modulation by Chemo- and Immunotherapy

Puntigam

Jeske

Götz

et al. 2020

IJMS

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Endogenous control mechanisms, including immune checkpoints and immunosuppressive cells, are exploited in the process of tumorigenesis to weaken the anti-tumor immune response. Cancer treatment by chemotherapy or immune checkpoint inhibition can lead to changes of checkpoint expression, which influences therapy success. Peripheral blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) were isolated from head and neck squamous cell carcinoma (HNSCC) patients (n = 23) and compared to healthy donors (n = 23). Immune checkpoint expression (programmed cell death ligand 1 (PD-1), tumor necrosis factor receptor (TNFR)-related (GITR), CD137, tumor necrosis factor receptor superfamily member 4 (TNFRSF4) (OX40), t-cell immunoglobulin and mucin-domain containing-3 (TIM3), B- and T-lymphocyte attenuator (BTLA), lymphocyte-activation gene 3 (LAG3)) was determined on immune cells by flow cytometry. PD-L1 expression was detected on tumor tissue by immunohistochemistry. Immune cells were treated with immuno- and chemotherapeutics to investigate treatment-specific change in immune checkpoint expression, in vitro. Specific changes of immune checkpoint expression were identified on PBL and TIL of HNSCC patients compared to healthy donors. Various chemotherapeutics acted differently on the expression of immune checkpoints. Changes of checkpoint expression were significantly less pronounced on regulatory T cells compared to other lymphocyte populations. Nivolumab treatment significantly reduced the receptor PD-1 on all analyzed T cell populations, in vitro. The specific immune checkpoint expression patterns in HNSCC patients and the investigated effects of immunomodulatory agents may improve the development and efficacy of targeted immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Immune Checkpoint Expression on Immune Cells of HNSCC Patients and Modulation by Chemo- and Immunotherapy

Puntigam

Jeske

Götz

et al. 2020

IJMS

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“…Gemcitabine is a nucleoside analog (2′,2′-difluorodeoxycytidine) used to treat patients with pancreatic, lung, breast, or bladder cancers. It has been occasionally combined with FOLFOX against colon cancer ( 234 ). Bacteria can metabolize the chemotherapeutic drug gemcitabine (2′,2′-difluorodeoxycytidine) into its inactive form, 2′,2′-difluorodeoxyuridine ( 211 ).…”

Section: Colon Cancer Therapies and Gut Microbiotamentioning

confidence: 99%

“…Camptothecin, a potent antineoplastic compound, poisons the catalytic cycle of human topoisomerase I. Camptothecin exhibited marked toxicity and poor bioavailability. Although its derivatives topotecan and CPT-11 (also called irinotecan) are now in clinical use ( 234 ), they still elicit pronounced side effects that limit efficacy. CPT-11 is one of the three commonly used chemotherapeutic agents for CRC ( 236 ).…”

Section: Colon Cancer Therapies and Gut Microbiotamentioning

confidence: 99%

Resolving the Paradox of Colon Cancer Through the Integration of Genetics, Immunology, and the Microbiota

et al. 2020

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While colorectal cancers (CRC) are paradigmatic tumors invaded by effector memory lymphocytes, the mechanisms accounting for the relative resistance of MSI negative CRC to immunogenic cell death mediated by oxaliplatin and immune checkpoint inhibitors has remained an open conundrum. Here, we propose the viewpoint where its microenvironmental contexture could be explained -at least in part- by macroenvironmental cues constituted by the complex interplay between the epithelial barrier, its microbial ecosystem, and the local immune system. Taken together this dynamic ménage-à-trois offers novel coordinated actors of the humoral and cellular immune responses actionable to restore sensitivity to immune checkpoint inhibition. Solving this paradox involves breaking tolerance to crypt stem cells by inducing the immunogenic apoptosis of ileal cells in the context of an ileal microbiome shifted towards immunogenic bacteria using cytotoxicants. This manoeuver results in the elicitation of a productive Tfh and B cell dialogue in mesenteric lymph nodes culminating in tumor-specific memory CD8+ T cell responses sparing the normal epithelium.

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“…CRC is the most common malignant tumor of digestive tract in the world, which seriously endangers people's health and quality of life. However, its pathogenesis has not been completely elucidated, and progression of CRC is a process that involves multiple genetic changes, multi-factor, multi-step process [17,18]. Previous studies indicate that one third of CRC patients may develop liver metastases, and most of CRC-related death is usually attributed to distant metastasis.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA expression profile in the N2 phenotype neutrophils of colorectal cancer and screen of putative key mircRNAs

Wang

Yang

Huang

et al. 2020

Preprint

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Objective: Colorectal cancer (CRC) is one of the most common malignant tumors in the digestive tract, which accounts for 10% of all the malignant tumors in the world. The aim of this study was to identify key genes and miRNAs in CRC diagnosis, prognosis, and therapy and to further explore the potential molecular mechanisms of CRC.Methods: The infiltration and metastasis of neutrophils in Primary colorectal cancer tissue and Paracancerous tissue were observed by immunohistochemical staining. After inducing N2 neutrophils with TGF-β1 in vitro, exosomes were extracted and sequenced, and then the expression differences of microRNAs were screened by using Agilent microRNA microarrays. The data were imported to the Web CARMA for differential expression analysis. The GO and KEGG enrichment analysis were performed using DIANA-MirPath v3.0 using Targetscan database. And the corresponding targets were imported into Gephi for network analysis. The expression level of differentially expressed microRNA using quantitative Realtime polymerase chain reaction (RT-PCR) was validated.Results: A total of 2 miRNAs were found to be associated with N2 neutrophils, in which the expression of hsa-miR-4780 was upregulated and the expression of hsa-miR-3938 was downregulated in N2 neutrophils, compared with the neutrophils. In addition, the results of miRNA-targets networks showed that the hsa-mir-3938 and hsa-mir-4780 could regulate TUSC1 and ZNF197. The expression level of hsa-miR-4780 and hsa-miR-3938 were validated in accordance with the results of RT-PCR.Conclusion: The hsa-mir-3938 and hsa-mir-4780 were differentially expressed between N2 neutrophils and neutrophils. Moreover, the regulation of TUSC1 and ZNF197 by these DEmiRNA established the theoretical basis for the mechanism of N2 type neutrophils regulating the invasion and metastasis of CRC cells, and provided the potential biomarker for prognosis for clinical treatment of CRC

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GOLFIG Chemo-Immunotherapy in Metastatic Colorectal Cancer Patients. A Critical Review on a Long-Lasting Follow-Up

Cited by 18 publications

References 45 publications

Immune Checkpoint Expression on Immune Cells of HNSCC Patients and Modulation by Chemo- and Immunotherapy

Immune Checkpoint Expression on Immune Cells of HNSCC Patients and Modulation by Chemo- and Immunotherapy

Resolving the Paradox of Colon Cancer Through the Integration of Genetics, Immunology, and the Microbiota

MicroRNA expression profile in the N2 phenotype neutrophils of colorectal cancer and screen of putative key mircRNAs

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