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Simple Summary: The lung is the second most common site of metastases in colorectal cancer (CRC). The aim of our study was to evaluate the prognostic value of CD3+ and CD8+ T-cell density based immune cell score (ICS) and PD-1/PD-L1 expression in resected pulmonary metastases of microsatellite stable CRC. The T-cell infiltration was higher in the first pulmonary metastases compared to primary tumour. Pulmonary metastases with high ICS had improved survival compared to low ICS after adjusting for confounders. High tumour cell PD-L1 expression was associated with favourable prognosis. Our results might have clinical feasibility in planning future therapies. 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. [ABSTRACT FROM AUTHOR]

Tumor necrosis has been reported to represent an independent prognostic factor in colorectal cancer, but its evaluation methods have not been described in sufficient detail to introduce tumor necrosis evaluation into clinical use. To study the potential of tumor necrosis as a prognostic indicator in colorectal cancer, criteria for 3 methods for its evaluation were defined: the average percentage method (tumor necrosis percentage of the whole tumor), the hotspot method (tumor necrosis percentage in a single hotspot), and the linear method (the diameter of the single largest necrotic focus). Cox regression models were used to calculate cancer-specific mortality hazard ratios (HRs) for tumor necrosis categories in 2 colorectal cancer cohorts with more than 1800 cases. For reproducibility assessment, 30 cases were evaluated by 9 investigators, and Spearman's rank correlation coefficients and Cohen's kappa coefficients were calculated. We found that all 3 methods predicted colorectal cancer-specific survival independent of other prognostic parameters, including disease stage, lymphovascular invasion, and tumor budding. The greatest multivariable HRs were observed for the average percentage method (cohort 1: HR for ≥ 40% vs. <3% 3.03, 95% CI, 1.93-4.78; cohort 2: HR for ≥ 40% vs. < 3% 2.97; 95% CI, 1.63-5.40). All 3 methods had high reproducibility, with the linear method showing the highest mean Spearman's correlation coefficient (0.91) and Cohen's kappa (0.70). In conclusion, detailed criteria for tumor necrosis evaluation were established. All 3 methods showed good reproducibility and predictive ability. The findings pave the way for the use of tumor necrosis as a prognostic factor in colorectal cancer., Competing Interests: Conflicts of Interest and Source of Funding: This study was funded by Cancer Foundation Finland (59-5619 to J.P.V.), Finnish Medical Foundation (6021 to J.P.V.; 6259 to M.K.), Oulu Medical Research Foundation (to M.K.), Sigrid Jusélius Foundation (230229 to J.P.V.), and Finnish State Research Funding (to M.J.M. and J.P.V.). T.T. Seppälä reports consultation fees from Amgen Finland, Tillots Pharma, and Nouscom, being a co-owner and CEO of Healthfund Finland Ltd, and a position in the Clinical Advisory Board and a minor shareholder of LS Cancer Diag Ltd. For the remaining authors, none were declared., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

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.