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 (2022). Image analysis reveals molecularly distinct patterns of TILs in NSCLC associated with treatment outcome. NPJ precision oncology, 6(1), p. 33. Springer Nature 10.1038/s41698-022-00277-5

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Tumour Pathology

Graduate School:

Graduate School for Health Sciences (GHS)

UniBE Contributor:

Zens, Philipp Immanuel and Berezowska, Sabina Anna

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

2397-768X

Publisher:

Springer Nature

Language:

English

Submitter:

Pubmed Import

Date Deposited:

08 Jun 2022 12:33

Last Modified:

08 Jun 2022 12:42

Publisher DOI:

10.1038/s41698-022-00277-5

PubMed ID:

35661148

BORIS DOI:

10.48350/170477

URI:

https://boris.unibe.ch/id/eprint/170477

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