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Image analysis reveals molecularly distinct patterns of TILs in NSCLC associated with treatment outcome.
Ding, Ruiwen; Prasanna, Prateek; Corredor, Germán; Barrera, Cristian; Zens, Philipp; Lu, Cheng; Velu, Priya; Leo, Patrick; Beig, Niha; Li, Haojia; Toro, Paula; Berezowska, Sabina; Baxi, Vipul; Balli, David; Belete, Merzu; Rimm, David L; Velcheti, Vamsidhar; Schalper, Kurt; Madabhushi, Anant.
Affiliation
  • Ding R; Case Western Reserve University, Cleveland, OH, USA.
  • Prasanna P; Stony Brook University, New York, NY, USA.
  • Corredor G; Case Western Reserve University, Cleveland, OH, USA.
  • Barrera C; Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA.
  • Zens P; Case Western Reserve University, Cleveland, OH, USA.
  • Lu C; Institute of Pathology, University of Bern, Bern, Switzerland.
  • Velu P; Graduate School for Health Sciences, University of Bern, Bern, Switzerland.
  • Leo P; Case Western Reserve University, Cleveland, OH, USA.
  • Beig N; Weill Cornell Medical College, New York, NY, USA.
  • Li H; Case Western Reserve University, Cleveland, OH, USA.
  • Toro P; Case Western Reserve University, Cleveland, OH, USA.
  • Berezowska S; Case Western Reserve University, Cleveland, OH, USA.
  • Baxi V; Case Western Reserve University, Cleveland, OH, USA.
  • Balli D; Institute of Pathology, University of Bern, Bern, Switzerland.
  • Belete M; Department of Laboratory Medicine and Pathology, Institute of Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Rimm DL; Bristol Myers Squibb, New York, NY, USA.
  • Velcheti V; Bristol Myers Squibb, New York, NY, USA.
  • Schalper K; Bristol Myers Squibb, New York, NY, USA.
  • Madabhushi A; Yale University, New Haven, CT, USA.
NPJ Precis Oncol ; 6(1): 33, 2022 Jun 03.
Article in En | MEDLINE | ID: mdl-35661148
Despite known histological, biological, and clinical differences between lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC), relatively little is known about the spatial differences in their corresponding immune contextures. Our study of over 1000 LUAD and LUSC tumors revealed that computationally derived patterns of tumor-infiltrating lymphocytes (TILs) on H&E images were different between LUAD (N = 421) and LUSC (N = 438), with TIL density being prognostic of overall survival in LUAD and spatial arrangement being more prognostically relevant in LUSC. In addition, the LUAD-specific TIL signature was associated with OS in an external validation set of 100 NSCLC treated with more than six different neoadjuvant chemotherapy regimens, and predictive of response to therapy in the clinical trial CA209-057 (n = 303). In LUAD, the prognostic TIL signature was primarily comprised of CD4+ T and CD8+ T cells, whereas in LUSC, the immune patterns were comprised of CD4+ T, CD8+ T, and CD20+ B cells. In both subtypes, prognostic TIL features were associated with transcriptomics-derived immune scores and biological pathways implicated in immune recognition, response, and evasion. Our results suggest the need for histologic subtype-specific TIL-based models for stratifying survival risk and predicting response to therapy. Our findings suggest that predictive models for response to therapy will need to account for the unique morphologic and molecular immune patterns as a function of histologic subtype of NSCLC.

Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Prognostic_studies / Risk_factors_studies Language: En Journal: NPJ Precis Oncol Year: 2022 Document type: Article Affiliation country: Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Prognostic_studies / Risk_factors_studies Language: En Journal: NPJ Precis Oncol Year: 2022 Document type: Article Affiliation country: Country of publication: