CD3+ and CD8+ T-Cell-Based Immune Cell Score and PD-(L)1 Expression in Pulmonary Metastases of Microsatellite Stable Colorectal Cancer

Topias Karjula; Hanna Elomaa; Anne Niskakangas; Olli Mustonen; Iiris Puro; Teijo Kuopio; Maarit Ahtiainen; Jukka-Pekka Mecklin; Toni T Seppälä; Erkki-Ville Wirta; Eero Sihvo; Juha P Väyrynen; Fredrik Yannopoulos; Olli Helminen

doi:10.3390/cancers15010206

CD3⁺ and CD8⁺ T-Cell-Based Immune Cell Score and PD-(L)1 Expression in Pulmonary Metastases of Microsatellite Stable Colorectal Cancer

Cancers (Basel). 2022 Dec 29;15(1):206. doi: 10.3390/cancers15010206.

Authors

Topias Karjula^{1

2}, Hanna Elomaa^{3

4}, Anne Niskakangas^{1

2}, Olli Mustonen^{1

2}, Iiris Puro^{1

2}, Teijo Kuopio^{3

5}, Maarit Ahtiainen⁵, Jukka-Pekka Mecklin^{4

6}, Toni T Seppälä^{7

8

9}, Erkki-Ville Wirta^{7

10}, Eero Sihvo¹¹, Juha P Väyrynen², Fredrik Yannopoulos^{1

12}, Olli Helminen^{1

2}

Affiliations

¹ Surgery Research Unit, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, 90014 Oulu, Finland.
² Cancer and Translational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, 90014 Oulu, Finland.
³ Department of Biological and Environmental Science, University of Jyväskylä, 40014 Jyväskylä, Finland.
⁴ Department of Education and Research, Central Finland Health Care District, 40620 Jyväskylä, Finland.
⁵ Department of Pathology, Central Finland Health Care District, 40620 Jyväskylä, Finland.
⁶ Faculty of Sport and Health Sciences, University of Jyväskylä, 40014 Jyväskylä, Finland.
⁷ Faculty of Medicine and Health Technology, Tampere University and TAYS Cancer Center, Tampere University Hospital, 33520 Tampere, Finland.
⁸ Department of Gastrointestinal Surgery, Helsinki University Central Hospital, University of Helsinki, 00290 Helsinki, Finland.
⁹ Applied Tumour Genomics, Research Program Unit, University of Helsinki, 00290 Helsinki, Finland.
¹⁰ Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, 33520 Tampere, Finland.
¹¹ Central Hospital of Central Finland, 40014 Jyväskylä, Finland.
¹² Department of Cardiothoracic Surgery, Oulu University Hospital, 90014 Oulu, Finland.

Abstract

The objective of this study was to evaluate the prognostic value of CD3⁺ and CD8⁺ based immune cell score (ICS), programmed death -1 (PD-1) and programmed death ligand -1 (PD-L1) in pulmonary metastases of proficient mismatch repair colorectal cancer (CRC) patients. A total of 101 pulmonary metastases and 62 primary CRC tumours were stained for CD3⁺, CD8⁺, PD-1 and PD-L1 expression. The prognostic value of ICS, PD-1/PD-L1 expression in 67 first pulmonary metastases and 61 primary CRC tumour was analysed. Comparative analysis was also performed between primary tumours and pulmonary metastases, as well as between T-cell densities and PD-1/PD-L1 expression. The 5-year overall survival rates of low, intermediate, and high ICS in pulmonary metastases were 10.0%, 25.5% and 47.0% (p = 0.046), respectively. Patients with high vs. low ICS in pulmonary metastases had a significantly better 5-year survival (adjusted HR 0.25, 95% CI 0.09-0.75, p = 0.013). High tumour cell PD-L1 expression in the pulmonary metastases was associated with improved survival (p = 0.024). Primary tumour CD8⁺ expression was significantly correlated with all T-cell densities in pulmonary metastases. Conclusion: The ICS evaluated from the resected pulmonary metastases of CRC showed significant prognostic value. High PD-L1 expression in pulmonary metastases is associated with favourable prognosis.

Keywords: colorectal carcinoma; programmed death 1; programmed death ligand 1; pulmonary metastases; tumour-infiltrating lymphocytes.

Grants and funding

This study was funded by Instrumentarium Science Foundation (O.H.), Mary and Georg C. Ehrnrooth Foundation (O.H.), Finnish State Research Funding (O.H.), and Cancer Foundation Finland (J.P.V.), J&A Erkko Foundation (J.-P.M.).