Prospective validation of a lymphocyte infiltration prognostic test in stage III colon cancer patients treated with adjuvant FOLFOX

Émile, Jean-François; Julié, Catherine; Malicot, Karine Le; Lepage, Côme; Dimet, Stéphanie; Boulagnon‐Rombi, Camille; Allard, Marc‐Antoine; Penault‐Llorca, Frédérique; Bennouna, Jaafar; Laurent‐Puig, Pierre; Thaler, Josef; Greil, Richard; Gaenzer, Johannes; Eisterer, Wolfgang; Tschmelitsch, Joerg; Keil, Felix; Samonigg, Hellmut; Zabernigg, August; Schmid, Franz A.; Steger, G.; Steinacher, Robert; Andel, Johannes; Jagdt, Björn; Lang, Alois; Fridrik, Michael A.; Függer, R.; Hofbauer, F; Woell, Ewald; Geissler, Dietmar; Lenauer, Alfred; Prager, Manfred; D’Haens, Geert R.; Demolin, Gauthier; Kerger, Joseph; Deboever, Guido; Ghillebert, G; Polus, Marc; Cutsem, Éric Van; Kalantari, Hassan Rezaie; Delaunoit, Thierry; Goeminne, Jean Charles.; Peeters, Marc; Vergauwe, Philippe; Houbiers, Ghislain; Humblet, Yves; Janssens, Jos; Schrijvers, Dirk; Vanderstraeten, Erik; Laethem, Jean‐Luc Van; Vermorken, Jan B.; Daele, Daniel Van; Ferrante, Michel; Forget, Fréd́eric; Hendlisz, Alain; Yilmaz, Mette Karen; Nielsen, Svend Erik; Vestermark, Lene Weber; Larsen, Jim S.; Zawadi, Mohamed-Ayman; Bouché, Olivier; Mineur, Laurent; Bennouna-Louridi, Jaafar; Dourthe, Louis Marie; Ychou, Marc; Boucher, Éveline; Taı̈eb, Julien; Pezet, Denis; Desseigne, Françoise; Ducreux, Michel; Texereau, Patrick; Miglianico, Laurent; Rougier, Philippe; Fratté, S.; Levaché, Charles-Briac; Merrouche, Yacine; Ellis, Stephen B.; Locher, Christophe; Ramée, Jean-François; Garnier, Claire; Viret, F.; Chauffert, Bruno; Cojean-Zelek, Isabelle; Martineau, Pierre; Lecaille, Cédric; Borel, Christian; Seitz, Jean‐François; Smith, Denis; Lombard‐Bohas, Catherine; Thewis, André; Gornet, Jean–Marc; Fein, Francine; Coulon-Sfairi, Marie-Aude; Kaminsky, Marie‐Christine; Lagasse, Jean-Paul; Luet, Dominique; Etienne, Pierre-Luc; Gasmi, Mohamed; Vanoli, André; Nguyen, Suzanne; Aparicio, Thomas; Perrier, H.; Stremsdoerfer, N; Laplaige, Philippe; Arsène, Dominique; Auby, Dominique; Bedenne, Laurent; Coriat, Romain; Denis, Bernard; Geoffroy, Patrick; Piot, G.; Bécouarn, Y.; Bordes, Gilbert; Deplanque, Gaël; Dupuis, Olivier; Fruge, F.; Guimbaud, Rosine; Lecomte, Thierry; Lledo, Gérard; Sobhani, I.; Asnacios, Amani; Azzedine, A.; Desauw, Christophe; Galais, Marie-Pierre; Gargot, D.; Lam, You-Heng; Abakar-Mahamat, Abakar; Berdah, Jean-François; Catteau, Sylviane; Clavero-Fabri, Marie-Christine; Codoul, Jean-François; Legoux, Jean-Louis; Goldfain, D; Guichard, P.; Verge, Denis Père; Provençal, J.; Vedrenne, B.; Brezault-Bonnet, Catherine; Cléau, D.; Desir, Jean-Paul; Fallik, David; Garcia, Bruno; Gaspard, M; Genet, Dominique; Hartwig, Johannes; Krummel, Yves; Budnik, T. Matysiak; Palascak-Juif, Vanessa; Randrianarivelo, Harizo; Rinaldi, Yves; Aleba, Albert; Darut-Jouve, Ariane; Gramont, Aimery de; Hamon, H.; Wendehenne, Frederic; Matzdorff, Axel; Ståhl, Michael; Schepp, Wolfgang; Burk, M.; Mueller, Lothar; Folprecht, Gunnar; Geißler, Michael; Mantovani-Loeffler, Luisa; Hoehler, Thomas; Asperger, Walter; Kroening, Hendrik; Weikersthal, Ludwig Fischer von; Fuxius, Stefan; Groschek, Matthias; Meiler, Johannes; Trarbach, Tanja; Rauh, Jacqueline; Ziegenhagen, Nicolas; Kretzschmar, Albrecht; Graeven, Ullrich; Nusch, Arnd; Wichert, Goetz von; Hofheinz, Ralf–Dieter; Kleber, Gerhard; Schmidt, Karl‐Heinz; Vehling-Kaiser, Ursula; Baum, Claudia; Schuette, Jochen; Haag, Georg Martin; Holtkamp, W.; Potenberg, Jochen; Reiber, T; Schliesser, Georg; Schmoll, Hans‐Joachim; Schneider-Kappus, Wolfgang; Abenhardt, Wolfgang; Denzlinger, Claudio; Henning, Jan; Marxsen, Bartscht; Derigs, Hans Guenter; Lambertz, Helmut; Becker-Boost, Ingulf; Caca, Karel; Constantin, Carolina; Decker, Thomas; Eschenburg, Henning; Gabius, Sigrun; Hebart, Holger; Hoffmeister, Albrecht; Horst, Heinz‐August; Kremers, Stephan; Leithaeuser, Malte; Mueller, Sebastian; Wagner, Siegfried; Daum, S; Schlegel, Frank; Stauch, Martina; Heinemann, Volker; Maiello, Evaristo; Latini, Luciano; Zaniboni, Alberto; Amadori, Dino; Aprile, Giuseppe; Barni, Sandro; Mattioli, Rodolfo; Martoni, Andrea; Passalacqua, Rodolfo; Nicolini, M.; Pasquini, E.; Rabbi, C.; Aitini, Enrico; Ravaioli, Alberto; Barone, Carlo; Biasco, Guido; Tamberi, Stefano; Gambi, Angelo; Verusio, Claudio; Marzola, Marina; Lelli, G.; Boni, C.; Cascinu, Stefano; Bidoli, Paolo; Vaghi, Massimo; Cruciani, Giorgio; Costanzo, Francesco Di; Sobrero, Alberto; Mini, Enrico; Petrioli, Roberto; Aglietta, Massimo; Alabiso, Oscar; Capuzzo, Federico; Falcone, Alfredo; Corsi, D.C.; Labianca, Roberto; Salvagni, Stefania; Chiara, Silvana; Ciuffreda, Libero; Ferraú, Francesco; Giuliani, Francesco; Lonardi, Sara; Gebbia, Nicola; Mantovani, Giovanni; Sanches, Evaristo; Mellidez, Juan Carlos; Santos, Pedro Paulo Albino dos; Freire, Joao; C, Sarmento; Costa, L.; Pinto, Antonio; Barroso, Sérgio; Santo, Jorge Espírito; Guedes, Fátima; Monteiro, Amelia Yuting; Sá, Anabela; Furtado, Irene; Salazar, Ramón; Aguilar, E. Aranda; Herrero, F. Rivera; Tabernero, Josep; Valera, Javier Sastre; Ayerbes, Manuel Valladares; Batlle, Jaime Feliú; Gil, Silvia; Esteve, Albert Abad; García-Girón, Carlos; Vivanco, Guillermo López; Salvia, Antonia Salud; Orduña, Vicente Alonso; García, Ruth Vera; Gallego, Javier González; Sureda, B. Massuti; Remón, Jordi; Aguilera, M.J. Safont; Nogueras, L. Cirera; Merino, Bernado Queralt; Castro, Cristina Grávalos; Prado, Purificación Martínez de; Pericay, C.; Figueiras, Manuel Constenla; Jordan, Inmaculada Guasch; Reina, Maria Jose Gome; Garcia, Amelia Lopez-Ladron; García-Ramos, Antonio Arrivi; Cervantes, Andrés; Martos, C. Fernández; Gaspar, Eugenio Marcuello; Montero, Ines Cabezas; Emperador, P. Escudero; Carbonero, Ana Leon; Castillo, Manuel Gallen; García, Teresa; Lopez, Jose Garcia; Flores, Encarnación González; Morales, Monica Guillot; Muñoz, Marta Llanos; Martín, Ana López; Maurel, Joan; Cámara, Juan Carlos; García, R. Dueñas; Salgado, Mercedes; Busquier, Isabel; Ruiz, Teresa Checa; Muñoa, Adelaida Lacasta; Aliguer, Miquel Nogue; Taranco, Amalia Velasco Ortiz de; Ureña, Miguel Mendez; Gaspà, Fernando Losa; Ponce, Jose Juan; Roig, C. Bosch; Jimenez, Pedro Valero; Brotons, Antonio Galán; Rodriguez, Santiago Albiol; Martinez, Jose Ales; Ruiz, Laura León; Ruiz, M.E. Terres; Bridgewater, John; Glynne-Jones, R.; Tahir, Saad; Hickish, Tamas; Cassidy, Jim; Samuel, Leslie

doi:10.1016/j.ejca.2017.04.025

Cited by 39 publications

(38 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results indicated that higher levels of TILs in the tumor tissue were associated with a better prognosis. In line with our results, many studies have revealed that the dysregulation of the immune system is associated with resistance to the FOLFOX regimen (Tanis et al, 2015;Limagne et al, 2016;Emile et al, 2017).…”

Section: Discussionsupporting

confidence: 92%

FBXW4 Acts as a Protector of FOLFOX-Based Chemotherapy in Metastatic Colorectal Cancer Identified by Co-Expression Network Analysis

et al. 2020

View full text Add to dashboard Cite

Background: FOLFOX chemotherapy is one of the most commonly used treatments for colorectal cancer (CRC) patients. However, the efficacy and tolerance of FOLFOX therapy varies between patients. The purpose of this study was to explore hub genes associated with primary chemotherapy-resistance and to explore the possible mechanisms involved from non-European patients.Method: A weighted gene co-expression network was constructed to identify gene modules associated with chemotherapy resistance in mCRC from China.Results: A Gene Array Chip was used to detect mRNA expression in 11 mCRC patients receiving preoperative FOLFOX chemotherapy. The immune response was associated with chemotherapy-resistance in microarray data. Through the use of WGCNA, we demonstrated that the crucial functions enriched in chemotherapy-resistance modules were cell proliferation, MAPK signaling pathways, and PI3K signaling pathways. Additionally, we identified and validated FBXW4 as a new effective predictor for chemotherapy sensitivity and a prognostic factor for survival of CRC patients by using our own data and GSE69657. Furthermore, a meta-analysis of 15 Gene Expression Omnibus-sourced datasets showed that FBXW4 messenger RNA levels were significantly lower in CRC tissues than in normal colon tissues. An analysis of the data from the R2: Genomics Analysis and Visualization Platform showed that low FBXW4 expression was correlated with a significantly worse event-and relapse-free survival. Gene set enrichment analysis showed that the mechanism of FBXW4-mediated chemotherapy resistance may involve the DNA replication signal pathway and the cell cycle.Conclusion: FBXW4 is associated with chemotherapy resistance and prognosis of CRC probably by regulating DNA replication signaling pathways and the cell cycle.

show abstract

Section: Discussionsupporting

confidence: 92%

FBXW4 Acts as a Protector of FOLFOX-Based Chemotherapy in Metastatic Colorectal Cancer Identified by Co-Expression Network Analysis

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In human CCR, several studies have shown that lymphocytic infiltration was a good prognostic factor, 38,49 even in the colorectal liver metastasis. We have shown an increase of T cells infiltration on distant tumor with complete treatment.…”

Section: Discussionmentioning

confidence: 99%

Local immunomodulation combined to radiofrequency ablation results in a complete cure of local and distant colorectal carcinoma

et al. 2019

Self Cite

View full text Add to dashboard Cite

Radiofrequency ablation (RFA) of colorectal liver metastases activates a specific T-cell response that is ineffective in avoiding recurrence. Recently, local immunomodulation garnered interests as a way to improve the immune response. We were interested in improving the RFA immune response priming to propose a curative treatment of colorectal cancer (CRC) based on antitumor immunity. First, we demonstrated that the RFA did not increase the tumor infiltrating lymphocytes in secondary distant tumors of patients and in mice model and could not avoid relapse. Remarkably, RFA and in situ immunomodulation with GM-CSF-BCG hydrogel induced complete cure of microscopic secondary lesions in mice, related to a strong specific immune response. Then, we demonstrated that the immune escape of large secondary lesions was reversed by addition of the systemic PD-1 blockade to the in situ immunomodulation. The lack of an effective distant immune response in patients treated with RFA confirmed the relevance of this new combination strategy. Increasing the in situ priming response of radiofrequency ablation provides effective adjuvants to induce an abscopal effect. In the case of large lesions, synergy between PD1 blockade inhibitor, ineffective alone or after single RFA, with in situ immunomodulation, could lead to reconsideration of the use of checkpoint inhibition in metastatic MSS CRC.

show abstract

“…Among them, the most relevant prognostic factor is the microsatellite instability (MSI) status of the tumor, reflecting a defect in DNA mismatch repair system . Other genetic alterations include BRAF and KRAS mutations, CpG island methylator phenotype (CIMP) and immune infiltrates …”

Section: Introductionmentioning

confidence: 99%

RNA sequencing reveals PNN and KCNQ1OT1 as predictive biomarkers of clinical outcome in stage III colorectal cancer patients treated with adjuvant chemotherapy

Mini

Lapucci

Perrone

et al. 2019

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

Five‐year overall survival of stage III colorectal cancer (CRC) patients treated with standard adjuvant chemotherapy (ACHT) is highly variable. Genomic biomarkers and/or transcriptomic profiles identified lack of adequate validation. Aim of our study was to identify and validate molecular biomarkers predictive of ACHT response in stage III CRC patients by a transcriptomic approach. From a series of CRC patients who received ACHT, two stage III extreme cohorts (unfavorable vs. favorable prognosis) were selected. RNA‐sequencing was performed from fresh frozen explants. Tumors were characterized for somatic mutations. Validation was performed in stage III CRC patients extracted from two GEO datasets. According to disease‐free survival (DFS), 108 differentially expressed genes (104/4 up/downregulated in the unfavorable prognosis group) were identified. Among 104 upregulated genes, 42 belonged to olfactory signaling pathways, 62 were classified as pseudogenes (n = 17), uncharacterized noncoding RNA (n = 10), immune response genes (n = 4), microRNA (n = 1), cancer‐related genes (n = 14) and cancer‐unrelated genes (n = 16). Three out of four down‐regulated genes were cancer‐related. Mutational status (i.e., RAS, BRAF, PIK3CA) did not differ among the cohorts. In the validation cohort, multivariate analysis showed high PNN and KCNQ1OT1 expression predictive of shorter DFS in ACHT treated patients (p = 0.018 and p = 0.014, respectively); no difference was observed in untreated patients. This is the first study that identifies by a transcriptomic approach and validates PNN and KCNQ1OT1 as molecular biomarkers predictive of chemotherapy response in stage III CRC patients. After a further validation in an independent cohort, PNN and KCNQ1OT1 evaluation could be proposed to prospectively identify stage III CRC patients benefiting from ACHT.

show abstract

Prospective validation of a lymphocyte infiltration prognostic test in stage III colon cancer patients treated with adjuvant FOLFOX

Cited by 39 publications

References 27 publications

FBXW4 Acts as a Protector of FOLFOX-Based Chemotherapy in Metastatic Colorectal Cancer Identified by Co-Expression Network Analysis

FBXW4 Acts as a Protector of FOLFOX-Based Chemotherapy in Metastatic Colorectal Cancer Identified by Co-Expression Network Analysis

Local immunomodulation combined to radiofrequency ablation results in a complete cure of local and distant colorectal carcinoma

RNA sequencing reveals PNN and KCNQ1OT1 as predictive biomarkers of clinical outcome in stage III colorectal cancer patients treated with adjuvant chemotherapy

Contact Info

Product

Resources

About