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Pre-Existing Tumoral B Cell Infiltration and Impaired Genome Maintenance Correlate with Response to Chemoradiotherapy in Locally Advanced Rectal Cancer

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Laboratorio de Terapia Molecular y Celular - Genocan, Fundación Instituto Leloir, Buenos Aires 1405, Argentina
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Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires 1425, Argentina
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Hospital de Gastroenterología Carlos Bonorino Udaondo, Buenos Aires 1264, Argentina
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Intergrupo Argentino para el Tratamiento de los Tumores Gastrointestinales (IATTGI), Buenos Aires 1264, Argentina
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Biomakers, Buenos Aires 1119, Argentina
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Imaxe, Buenos Aires 1120, Argentina
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Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas (CIDIE), Universidad Católica de Córdoba, Córdoba 5016, Argentina
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Centro de Investigaciones Inmunológicas Básicas y Aplicadas (CINIBA), Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata 1900, Argentina
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2020, 12(8), 2227; https://doi.org/10.3390/cancers12082227
Received: 19 May 2020 / Revised: 20 June 2020 / Accepted: 1 July 2020 / Published: 10 August 2020
(This article belongs to the Section Cancer Biomarkers)
Locally advanced rectal cancer (LARC) remains a medical challenge. Reliable biomarkers to predict which patients will significantly respond to neoadjuvant chemoradiotherapy (nCRT) have not been identified. We evaluated baseline genomic and transcriptomic features to detect differences that may help predict response to nCRT. Eligible LARC patients received nCRT (3D-LCRT 50.4 Gy plus capecitabine 825 mg/m2/bid), preceded by three cycles of CAPOX in high systemic-relapse risk tumors, and subsequent surgery. Frozen tumor biopsies at diagnosis were sequenced using a colorectal cancer panel. Transcriptomic data was used for pathway and cell deconvolution inferential algorithms, coupled with immunohistochemical validation. Clinical and molecular data were analyzed according to nCRT outcome. Pathways related to DNA repair and proliferation (p < 0.005), and co-occurrence of RAS and TP53 mutations (p = 0.001) were associated with poor response. Enrichment of expression signatures related to enhanced immune response, particularly B cells and interferon signaling (p < 0.005), was detected in good responders. Immunohistochemical analysis of CD20+ cells validated the association of good response with B cell infiltration (p = 0.047). Findings indicate that the presence of B cells is associated with successful tumor regression following nCRT in LARC. The prevalence of simultaneous RAS and TP53 mutations along with a proficient DNA repair system that may counteract chemoradio-induced DNA damage was associated with poor response. View Full-Text
Keywords: rectal cancer; immune response; gene expression; neoadjuvant chemoradiotherapy; biomarker rectal cancer; immune response; gene expression; neoadjuvant chemoradiotherapy; biomarker
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MDPI and ACS Style

Sendoya, J.M.; Iseas, S.; Coraglio, M.; Golubicki, M.; Robbio, J.; Salanova, R.; Kujaruk, M.; Mikolaitis, V.; Rizzolo, M.; Ruiz, G.; Cabanne, A.; Gualdrini, U.; Mendez, G.; Hirmas, S.; Rotondaro, C.; Viglino, J.; Eleta, M.; Fernandez, E.; Abba, M.; Podhajcer, O.; Roca, E.; Llera, A.S. Pre-Existing Tumoral B Cell Infiltration and Impaired Genome Maintenance Correlate with Response to Chemoradiotherapy in Locally Advanced Rectal Cancer. Cancers 2020, 12, 2227. https://doi.org/10.3390/cancers12082227

AMA Style

Sendoya JM, Iseas S, Coraglio M, Golubicki M, Robbio J, Salanova R, Kujaruk M, Mikolaitis V, Rizzolo M, Ruiz G, Cabanne A, Gualdrini U, Mendez G, Hirmas S, Rotondaro C, Viglino J, Eleta M, Fernandez E, Abba M, Podhajcer O, Roca E, Llera AS. Pre-Existing Tumoral B Cell Infiltration and Impaired Genome Maintenance Correlate with Response to Chemoradiotherapy in Locally Advanced Rectal Cancer. Cancers. 2020; 12(8):2227. https://doi.org/10.3390/cancers12082227

Chicago/Turabian Style

Sendoya, Juan M.; Iseas, Soledad; Coraglio, Mariana; Golubicki, Mariano; Robbio, Juan; Salanova, Ruben; Kujaruk, Mirta; Mikolaitis, Vanesa; Rizzolo, Mariana; Ruiz, Gonzalo; Cabanne, Ana; Gualdrini, Ubaldo; Mendez, Guillermo; Hirmas, Stella; Rotondaro, Cecilia; Viglino, Julieta; Eleta, Martín; Fernandez, Elmer; Abba, Martín; Podhajcer, Osvaldo; Roca, Enrique; Llera, Andrea S 2020. "Pre-Existing Tumoral B Cell Infiltration and Impaired Genome Maintenance Correlate with Response to Chemoradiotherapy in Locally Advanced Rectal Cancer" Cancers 12, no. 8: 2227. https://doi.org/10.3390/cancers12082227

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