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Article

Integrated Clinical, Molecular and Immunological Characterization of Pulmonary Sarcomatoid Carcinomas Reveals an Immune Escape Mechanism That May Influence Therapeutic Strategies

by
Susann Stephan-Falkenau
1,*,
Anna Streubel
1,
Thomas Mairinger
1,
Torsten-Gerriet Blum
2,
Jens Kollmeier
2,
Fabian D. Mairinger
3,4,
Torsten Bauer
2,
Joachim Pfannschmidt
5,
Manuel Hollmann
1 and
Michael Wessolly
3,4
1
Institute for Tissue Diagnostics, MVZ at Helios Klinikum Emil von Behring, 14165 Berlin, Germany
2
Department of Pneumology, Heckeshorn Lung Clinic, Helios Klinikum Emil von Behring, 14165 Berlin, Germany
3
Institute of Pathology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
4
German Cancer Consortium (DKTK), Partner Site University Hospital Essen, 45147 Essen, Germany
5
Department of Thoracic Surgery, Heckeshorn Lung Clinic, Helios Klinikum Emil von Behring, 14165 Berlin, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(13), 10558; https://doi.org/10.3390/ijms241310558
Submission received: 22 May 2023 / Revised: 16 June 2023 / Accepted: 21 June 2023 / Published: 23 June 2023
(This article belongs to the Special Issue Tackle Lung Cancer by Means of Novel Immunotherapeutic Strategies)
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Abstract

Pulmonary sarcomatoid carcinoma (PSC) has highly aggressive biological behaviour and poor clinical outcomes, raising expectations for new therapeutic strategies. We characterized 179 PSC by immunohistochemistry, next-generation sequencing and in silico analysis using a deep learning algorithm with respect to clinical, immunological and molecular features. PSC was more common in men, older ages and smokers. Surgery was an independent factor (p < 0.01) of overall survival (OS). PD-L1 expression was detected in 82.1% of all patients. PSC patients displaying altered epitopes due to processing mutations showed another PD-L1-independent immune escape mechanism, which also significantly influenced OS (p < 0.02). The effect was also maintained when only advanced tumour stages were considered (p < 0.01). These patients also showed improved survival with a significant correlation for immunotherapy (p < 0.05) when few or no processing mutations were detected, although this should be interpreted with caution due to the small number of patients studied. Genomic alterations for which there are already approved drugs were present in 35.4% of patients. Met exon 14 skipping was found more frequently (13.7%) and EGFR mutations less frequently (1.7%) than in other NSCLC. In summary, in addition to the divergent genomic landscape of PSC, the specific immunological features of this prognostically poor subtype should be considered in therapy stratification.
Keywords: pulmonary sarcomatoid carcinoma; PSC; NSCLC; precision oncology; targeted therapy; immunotherapy; MET Exon 14 skipping mutations; PD-L1 expression; processing escape pulmonary sarcomatoid carcinoma; PSC; NSCLC; precision oncology; targeted therapy; immunotherapy; MET Exon 14 skipping mutations; PD-L1 expression; processing escape

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MDPI and ACS Style

Stephan-Falkenau, S.; Streubel, A.; Mairinger, T.; Blum, T.-G.; Kollmeier, J.; Mairinger, F.D.; Bauer, T.; Pfannschmidt, J.; Hollmann, M.; Wessolly, M. Integrated Clinical, Molecular and Immunological Characterization of Pulmonary Sarcomatoid Carcinomas Reveals an Immune Escape Mechanism That May Influence Therapeutic Strategies. Int. J. Mol. Sci. 2023, 24, 10558. https://doi.org/10.3390/ijms241310558

AMA Style

Stephan-Falkenau S, Streubel A, Mairinger T, Blum T-G, Kollmeier J, Mairinger FD, Bauer T, Pfannschmidt J, Hollmann M, Wessolly M. Integrated Clinical, Molecular and Immunological Characterization of Pulmonary Sarcomatoid Carcinomas Reveals an Immune Escape Mechanism That May Influence Therapeutic Strategies. International Journal of Molecular Sciences. 2023; 24(13):10558. https://doi.org/10.3390/ijms241310558

Chicago/Turabian Style

Stephan-Falkenau, Susann, Anna Streubel, Thomas Mairinger, Torsten-Gerriet Blum, Jens Kollmeier, Fabian D. Mairinger, Torsten Bauer, Joachim Pfannschmidt, Manuel Hollmann, and Michael Wessolly. 2023. "Integrated Clinical, Molecular and Immunological Characterization of Pulmonary Sarcomatoid Carcinomas Reveals an Immune Escape Mechanism That May Influence Therapeutic Strategies" International Journal of Molecular Sciences 24, no. 13: 10558. https://doi.org/10.3390/ijms241310558

APA Style

Stephan-Falkenau, S., Streubel, A., Mairinger, T., Blum, T.-G., Kollmeier, J., Mairinger, F. D., Bauer, T., Pfannschmidt, J., Hollmann, M., & Wessolly, M. (2023). Integrated Clinical, Molecular and Immunological Characterization of Pulmonary Sarcomatoid Carcinomas Reveals an Immune Escape Mechanism That May Influence Therapeutic Strategies. International Journal of Molecular Sciences, 24(13), 10558. https://doi.org/10.3390/ijms241310558

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