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Infiltration of CD3+ and CD8+ lymphocytes in association with inflammation and survival in pancreatic cancer.
Tushoski-Alemán, Gerik W; Herremans, Kelly M; Underwood, Patrick W; Akki, Ashwin; Riner, Andrea N; Trevino, Jose G; Han, Song; Hughes, Steven J.
Afiliación
  • Tushoski-Alemán GW; Department of Surgery, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
  • Herremans KM; Department of Surgery, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
  • Underwood PW; Department of Surgery, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
  • Akki A; Department of Pathology, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
  • Riner AN; Department of Surgery, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
  • Trevino JG; Department of Surgery, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
  • Han S; Department of Surgery, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
  • Hughes SJ; Department of Surgery, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
PLoS One ; 19(2): e0297325, 2024.
Article en En | MEDLINE | ID: mdl-38346068
ABSTRACT

BACKGROUND:

Pancreatic ductal adenocarcinomas (PDAC) have heterogeneous tumor microenvironments relatively devoid of infiltrating immune cells. We aimed to quantitatively assess infiltrating CD3+ and CD8+ lymphocytes in a treatment-naïve patient cohort and assess associations with overall survival and microenvironment inflammatory proteins.

METHODS:

Tissue microarrays were immunohistochemically stained for CD3+ and CD8+ lymphocytes and quantitatively assessed using QuPath. Levels of inflammation-associated proteins were quantified by multiplexed, enzyme-linked immunosorbent assay panels on matching tumor and tissue samples.

RESULTS:

Our findings revealed a significant increase in both CD3+ and CD8+ lymphocytes populations in PDAC compared with non-PDAC tissue, except when comparing CD8+ percentages in PDAC versus intraductal papillary mucinous neoplasms (IPMN) (p = 0.5012). Patients with quantitatively assessed CD3+ low tumors (lower 50%) had shorter survival (median 273 days) compared to CD3+ high tumors (upper 50%) with a median overall survival of 642.5 days (p = 0.2184). Patients with quantitatively assessed CD8+ low tumors had significantly shorter survival (median 240 days) compared to CD8+ high tumors with a median overall survival of 1059 days (p = 0.0003). Of 41 proteins assessed in the inflammation assay, higher levels of IL-1B and IL-2 were significantly associated with decreased CD3+ infiltration (r = -0.3704, p = 0.0187, and r = -0.4275, p = 0.0074, respectively). Higher levels of IL-1B were also significantly associated with decreased CD8+ infiltration (r = -0.4299, p = 0.0045), but not IL-2 (r = -0.0078, p = 0.9616). Principal component analysis of the inflammatory analytes showed diverse inflammatory responses in PDAC.

CONCLUSION:

In this work, we found a marked heterogeneity in infiltrating CD3+ and CD8+ lymphocytes and individual inflammatory responses in PDAC. Future mechanistic studies should explore personalized therapeutic strategies to target the immune and inflammatory components of the tumor microenvironment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos