PD-L1 expression as a prognostic factor for postoperative outcomes in pleural mesothelioma

Introduction

Pleural mesothelioma (PM) is an uncommon and highly aggressive malignancy caused primarily by asbestos exposure. Despite therapeutic advances, PM remains a challenging disease, with median survival rates typically ranging from 14 to 28 months post-treatment (1,2). Current clinical recommendations support a multimodal therapeutic approach, incorporating surgery for carefully selected patients (3). However, the prognosis often remains poor and surgical risks are significant (1). Reliable biomarkers that can predict treatment efficacy and guide therapeutic decision-making are urgently needed.

One potential biomarker is programmed death-ligand 1 (PD-L1) on tumor cells, which binds to programmed cell death protein 1 (PD-1) on T cells. This interaction suppresses T cell activation and proliferation, allowing tumor cells to evade immune surveillance. PD-L1 expression is associated with poor prognosis and resistance to conventional therapies in various cancers (4-7), and similar associations have been observed in PM (8-10). However, there is a paucity of data on the prognostic significance of PD-L1 expression in patients undergoing surgical resection and, in particular, pleurectomy/decortication (P/D), the current standard surgical procedure for curative-intent treatment (11-14).

This study evaluated the prognostic impact of tumor cell PD-L1 expression in patients with PM underwent curative-intent surgery at our institution. By examining PD-L1 expression in patients who have undergone P/D, we sought to assess its potential as a prognostic biomarker for survival and disease progression. We present this article in accordance with the REMARK reporting checklist (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-621/rc).

Methods

Patient cohort and study design

This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was conducted with the approval of the Ethics Committee of the University of Occupational and Environmental Health, Japan (approval No. 19-042). Informed consent was not required due to the retrospective nature of this study. From January 2012 to December 2022, a total of 67 patients underwent P/D at our institution. After excluding cases involving salvage surgery (n=5) and cases where PD-L1 evaluation was not possible (n=4), 58 cases were included in this retrospective analysis.

Preoperative assessment included evaluation of the patient’s general condition, including Eastern Cooperative Oncology Group (ECOG) performance status, laboratory investigations, cardiopulmonary function testing, and imaging studies. Surgical resection was indicated for patients with clinical stage T1–3N0–1M0 disease, based on 8^th edition of the International Mesothelioma Interest Group staging system (15). Our institutional treatment approach consisted of P/D, followed by adjuvant therapy (16).

Assessment of PD-L1 expression in surgical specimens

PD-L1 expression was evaluated in our laboratory using formalin-fixed, paraffin-embedded tumor specimens obtained from P/D procedures. Tissue samples were sectioned into serial 4-µm slices and processed for immunohistochemical staining according to established protocols (17,18), using an anti-human PD-L1 antibody (clone E1L3N; dilution 1:200; Cell Signaling Technology, Danvers, MA, USA). Sections were subsequently counterstained with hematoxylin to visualize cell nuclei. PD-L1 expression was assessed exclusively in tumor cells, based on the proportion of cells exhibiting membranous staining, defined as the tumor proportion score (TPS). Two independent investigators, blinded to clinical information, evaluated each specimen. In cases of interobserver discrepancy, consensus was achieved through joint slide review and discussion. As there are no universally accepted cut-off values for PD-L1 expression in PM, we adopted thresholds based on previous studies in the field (8,9,19). Specifically, TPS ≥1% was used to define PD-L1 positivity, and TPS ≥50% to define high expression.

Statistical analysis

Categorical variables were compared using Pearson’s χ² test or Fisher’s exact test, as appropriate based on expected cell counts. Continuous variables were analyzed using Student’s t-test or Welch’s t-test for normally distributed data, and the Mann-Whitney U test for non-normally distributed data. OS was defined as the interval from the date of surgery to death from any cause or last follow-up, and relapse-free survival (RFS) as the time from surgery to the first documented relapse, death, or last follow-up. Survival curves were estimated using the Kaplan-Meier method, with 95% confidence intervals (CIs) provided. Differences in survival between groups were evaluated using the log-rank test. Prognostic factors were further examined using a Cox proportional hazards model. Clinically relevant factors were pre-specified and assessed in the univariable analysis. Multivariable models included variables with P<0.10 in the univariable analysis. A P value <0.05 was considered statistically significant. All analyses were performed using SPSS software (version 28.0, IBM Corp, Armonk, NY, USA).

Results

Clinical characteristics and surgical outcomes

As summarized in Table 1, the majority of patients were male (89.7%), with a median age of 69 years (range, 47–82 years). Histologically, 42 patients had epithelioid, 6 had biphasic, and 10 had sarcomatoid subtypes of PM. Clinical staging was IA in 26, IB in 24, II in 6, and IIIB in 2 cases. All patients underwent P/D, and combined resection of the pericardium or diaphragm (extended P/D) was performed in 51 cases (87.9%). Macroscopic complete resection (MCR) was achieved in 91.4%. The postoperative morbidity rate was 74.1%. There was no 30-day mortality, while the 90-day mortality rate was 1.7% (1 case). Pathological staging revealed 8 patients with stage IA, 29 with IB, 2 with II, 8 with IIIA, and 11 with IIIB. PD-L1 status was 36.2% for TPS 0%, 44.8% for TPS 1–49%, and 19.0% for TPS ≥50%. PD-L1 positive status (≥1%) and PD-L1 high expression (≥50%) were associated with non-epithelioid histology (TPS ≥1%: epithelioid 59.5%, non-epithelioid 75.0%; TPS ≥50%: epithelioid 11.9%, non-epithelioid 37.5%).

Survival analysis

The median follow-up period was 30.0 months (range, 2.7–152.9 months). During this period, 28 (48.3%) died and 43 (74.1%) experienced relapses. Of those who experienced relapses, 34 (79.1%) experienced locoregional relapse, and 9 (20.9%) had both locoregional and distant relapses. The median OS for all patients was 37.3 months (95% CI: 26.0–48.6), and the median RFS was 14.6 months (95% CI: 11.8–17.4) (Figure S1A,S1B). In the epithelioid subtype, the median OS was 61.6 months (95% CI: 31.5–91.7), and the median RFS was 16.5 months (95% CI: 3.5–29.5). For the non-epithelioid subtype, the median OS was 25.3 months (95% CI: 7.3–43.4), and the median RFS was 6.9 months (95% CI: 5.1–8.7). The epithelioid subtype demonstrated significantly better outcomes (OS: P=0.002, RFS: P<0.001) (Figure S1C,S1D).

Prognostic impact of PD-L1 expression

Table S1 presents the clinical characteristics and surgical outcomes stratified by PD-L1 expression status (TPS ≥1% vs. TPS 0% and TPS ≥50% vs. TPS <50%). When analyzed according to PD-L1 expression, the median OS was 77.0 months (95% CI: 20.7–133.2), 41.0 months (95% CI: 22.7–59.3), and 25.3 months (95% CI: 7.1–42.9) for TPS 0%, 1–49%, and ≥50%, respectively. The median RFS was 34.3 months (95% CI: 22.8–45.8), 13.2 months (95% CI: 7.4–19.0), and 6.7 months (95% CI: 3.6–9.8) for TPS 0%, 1–49%, and ≥50%, respectively (Figure 1A,1B). Lower PD-L1 expression was significantly associated with improved outcomes (OS: P=0.041, RFS: P=0.002). Specifically, for PD-L1 ≥1% vs. 0%; OS: P=0.17, and RFS: P<0.001; for PD-L1 ≥50% vs. <50%, OS: P=0.02 and RFS: P=0.001 (Figure S2).

Figure 1 Overall survival and relapse-free survival after P/D stratified by PD-L1 expression. TPS: 0%, 1–49%, ≥50%. (A,B) All patients; (C,D) epithelioid subtype; (E,F) non-epithelioid subtype. P/D, pleurectomy/decortication; PD-L1, programmed death-ligand 1; TPS, tumor proportion score.

Within the epithelioid subtype, the median OS for TPS 0%, 1–49%, and ≥50% was 77.0 months (95% CI: 0–162.0), 41.4 months (95% CI: 0.0–92.8), and 35.6 months (95% CI: 0.5–70.7), respectively. The median RFS for these groups was 37.0 months (95% CI: 0.0–89.0), 13.7 months (95% CI: 12.5–14.9), and 10.5 months (95% CI: 0.0–36.1), respectively (Figure 1C,1D). Lower PD-L1 expression was associated with better RFS in the epithelioid subtype (OS: P=0.39, RFS: P=0.02). For PD-L1 ≥1% vs. 0%, OS: P=0.26 and RFS: P=0.004; for PD-L1 ≥50% vs. <50%, OS: P=0.28 and RFS: P=0.36 (Figure S3). In the non-epithelioid subtype, the median OS was 15.9 months (95% CI: 0.0–32.0) for TPS 0%, 31.9 months (95% CI: 3.6–60.2) for TPS 1–49%, and 13.6 months (95% CI: 0.0–38.6) for TPS ≥50%. The median RFS was 11.2 months (95% CI: 0.0–23.4) for TPS 0%, 7.6 months (95% CI: 2.9–12.3) for TPS 1–49%, and 4.0 months (95% CI: 0.5–7.5) for TPS ≥50% (Figure 1E,1F). In the non-epithelioid subtype, no significant association was found between PD-L1 expression and OS and RFS outcomes (OS: P=0.11, RFS: P=0.75). For PD-L1 ≥1% vs. 0%, OS: P=0.30 and RFS: P=0.51; for PD-L1 ≥50% vs. <50%, OS: P=0.15 and RFS: P=0.55 (Figure S4).

The univariable analysis, which included age, sex, tumor location, procedure, histological subtype, pathological stage, and adjuvant chemotherapy, revealed that PD-L1 expression was a significant prognostic factor for OS (P=0.02: <50% vs. ≥50%) or RFS (P=0.001: ≥1% vs. 0%; P=0.03: <50% vs. ≥50%) (Table 2). In the multivariable analysis including PD-L1 expression (≥1% vs. 0%, model 1), PD-L1 status was an independent prognostic factor for RFS [hazard ratio (HR), 0.37; 95% CI: 0.18–0.76; P=0.007]. However, including PD-L1 expression (<50% vs. ≥50%, model 2), PD-L1 status was not identified as an independent prognostic factor for OS (HR, 0.61; 95% CI: 0.21–1.75; P=0.36) and RFS (HR, 0.46; 95% CI: 0.20–1.04; P=0.06) (Table 3). To further explore the prognostic value of PD-L1 expression in a clinically relevant subgroup, we performed a supplementary multivariable analysis restricted to patients with epithelioid histology. PD-L1 status (≥1% vs. 0%, model 1) was also an independent prognostic factor for RFS [hazard ratio (HR), 0.35; 95% CI: 0.15–0.81; P=0.01] (Tables S2,S3), suggesting potential utility of PD-L1 as a prognostic marker even within this histological subtype.

Post-relapse course

Of the 43 patients who experienced postoperative relapse, 24 received ICIs (nivolumab monotherapy: 20, combination of ipilimumab and nivolumab: 4). Three patients were managed with best supportive care. Over a median follow-up period of 9.6 months (range, 0.2–53.4 months), the median post-relapse survival was 12.2 months (95% CI: 2.5–22.0). In contrast to surgical outcomes, when stratified by PD-L1 expression, patients with TPS ≥1% had significantly better survival (P=0.006) than those with TPS 0% [18.4 months (95% CI: 9.7–27.1) vs. 5.0 months (95% CI: 1.4–8.6), respectively] (Figure 2A).

Figure 2 Post-relapse survival stratified by PD-L1 expression regardless of ICIs use (A), ICIs treatment status (B), ICIs treatment status in patients with TPS 0% (C), and ≥1% (D). ICIs, immune checkpoint inhibitors; PD-L1, programmed death-ligand 1; TPS, tumor proportion score.

Although not statistically significant, patients treated with ICIs showed a trend toward better prognosis (P=0.12) than those not treated with ICIs [18.4 months (95% CI: 8.2–28.6) vs. 7.7 months (95% CI: 0–17.7)] (Figure 2B). This trend was observed regardless of PD-L1 expression status. In patients with TPS 0%, the median survival was 5.0 months (95% CI: 0.20–9.8) in the ICIs group compared to 4.0 months (95% CI: 0.16–7.8) in the non-ICIs group (P=0.25). In patients with TPS ≥1%, the median survival was 19.6 months (95% CI: 0.17–39.0) in the ICIs group compared to 12.2 months (95% CI: 0–29.7) in the non-ICIs group (P=0.22) (Figure 2C,2D).

Discussion

Our findings suggest that tumor cell PD-L1 expression in patients with PM undergoing curative-intent P/D may significantly influence postoperative prognosis and relapse risk. Lower PD-L1 expression was associated with significantly better OS and RFS, indicating the potential value of a standard multimodal approach including P/D. Conversely, PD-L1-positive patients, who tend to experience worse outcomes, require careful postoperative follow-up and might benefit from non-surgical treatment or perioperative ICIs therapy. Furthermore, by evaluating post-relapse survival in relation to PD-L1 expression and ICIs use, our study provides novel insights into the optimal management of patients after relapse.

Compared to the MARS2 trial (1) and real-world clinical data from Japan (13), our study found more favorable OS and RFS outcomes, which are likely due to a high rate of MCR, excellent surgical safety, and consistent use of postoperative adjuvant chemotherapy (14,20). When stratified by PD-L1 expression, PD-L1-negative patients had better OS and RFS than PD-L1 positive patients. While previous reports frequently noted that PD-L1 impacts OS, its association with RFS or progression-free survival has been less consistently addressed (8-11). Notably, Lee et al. (12) demonstrated a significant association between PD-L1 expression and RFS in patients who underwent MCR, consistent with our findings. However, in contrast to our results, their study reported a more pronounced difference in OS than in RFS. In our study, PD-L1-positive patients demonstrated significantly better post-relapse survival, which may account for the more marked difference in RFS than in OS. One possible explanation for this discrepancy is the availability of ICIs as a treatment option post-relapse in our cohort. This might have mitigated the OS difference in PD-L1-positive patients, thereby aligning their outcomes more closely with those of PD-L1-negative patients. Indeed, subgroup analysis stratified by immunotherapy exposure revealed a trend toward improved post-relapse survival in patients who received ICIs, particularly among those with PD-L1-positive tumors. However, the differences were not statistically significant, calling for larger patient cohort studies to validate these findings.

Consistent with prior reports (19,21), PD-L1 expression was higher in non-epithelioid subtypes, suggesting a role of histological subtypes in determining prognosis. Given that surgery is typically performed in epithelioid PM cases due to better treatment outcomes (3), we analyzed outcomes based on histological subtype. While PD-L1 expression was associated with prognosis in epithelioid PM, no such association was observed in non-epithelioid PM, suggesting a limited surgery benefit in non-epithelioid subtypes regardless of PD-L1 status. In epithelioid PM, PD-L1 status was closely related to prognosis, indicating that patients with low PD-L1 expression likely benefit from multimodal treatment including surgery, while those with high PD-L1 expression may require careful postoperative follow-up and consideration of alternative therapies.

PD-L1 is often recognized as a biomarker for predicting the efficacy of ICIs (22-24), administered either alone or in combination with chemotherapy (25). Our findings support the potential importance of perioperative ICIs therapy (26,27).

In the multivariable analysis, PD-L1 status (0% vs. ≥1%) emerged as a statistically significant prognostic factor for postoperative prognosis in PM, particularly regarding relapse after surgery. Although PD-L1 status was not a statistically significant predictor of OS, its role in guiding treatment strategies may enhance overall treatment outcomes in PM. These findings highlight the importance of considering PD-L1 expression when devising postoperative management plans to improve long-term prognosis.

Our study has limitations. First, it was conducted at a single-institution study with a limited sample size, which may have introduced selection bias. Second, PD-L1 expression was measured using postoperative specimens, which may not fully reflect preoperative PD-L1 status. PD-L1 expression may change due to surgical or treatment-related factors; thus, preoperative assessment would offer a more accurate picture of PD-L1 as a prognostic marker. Third, the proportion of sarcomatoid mesothelioma in our cohort (17%) was higher than that typically reported in surgical case series (1,13). As sarcomatoid histology is frequently associated with higher PD-L1 expression (19,21), this histologic distribution may have influenced our findings regarding PD-L1 as a prognostic biomarker and could limit the generalizability of our results. Fourth, intratumoral heterogeneity of PD-L1 expression may limit its reliability and reproducibility as a prognostic biomarker in PM. Sampling bias or spatial variability within the tumor may lead to misclassification, and variability among different testing platforms could further affect reproducibility of our results (28). Finally, future studies should incorporate other emerging prognostic factors such as other immune-related factors (e.g., human leukocyte antigen class I) and tumor-infiltrating lymphocytes, and tumor mutational burden (29-32) for a more comprehensive analysis.

Conclusions

Our study identifies PD-L1 expression in tumor cells as a prognostic factor in patients with PM undergoing P/D, with lower PD-L1 expression associated with better outcomes. PD-L1 could serve as a biomarker to help guide treatment decisions, with PD-L1-positive patients potentially benefiting from enhanced postoperative monitoring and perioperative ICIs therapy. Moreover, PD-L1 could potentially help guide personalized treatment in PM. The potential of preoperative PD-L1 assessment in optimizing treatment strategies and the mechanistic role of PD-L1 in PM progression should be further explored.

Acknowledgments

The authors thank all the patients who participated in this study.

Footnote

Reporting Checklist: The authors have completed the REMARK checklist. Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-621/rc

Data Sharing Statement: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-621/dss

Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-621/prf

Funding: This work was supported by JSPS KAKENHI (grant No. JP24K19445).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-621/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments and approved by the Ethics Committee of the University of Occupational and Environmental Health, Japan (approval No. 19-042). Informed consent was not required due to the retrospective nature of this study.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Lim E, Waller D, Lau K, et al. Extended pleurectomy decortication and chemotherapy versus chemotherapy alone for pleural mesothelioma (MARS 2): a phase 3 randomised controlled trial. Lancet Respir Med 2024;12:457-66. [Crossref] [PubMed]
2. Baas P, Scherpereel A, Nowak AK, et al. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet 2021;397:375-86. [Crossref] [PubMed]
3. Popat S, Baas P, Faivre-Finn C, et al. Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up Ann Oncol 2022;33:129-42. [Crossref] [PubMed]
4. Wang A, Wang HY, Liu Y, et al. The prognostic value of PD-L1 expression for non-small cell lung cancer patients: a meta-analysis. Eur J Surg Oncol 2015;41:450-6. [Crossref] [PubMed]
5. Huang W, Ran R, Shao B, et al. Prognostic and clinicopathological value of PD-L1 expression in primary breast cancer: a meta-analysis. Breast Cancer Res Treat 2019;178:17-33. [Crossref] [PubMed]
6. Kollmann D, Schweiger T, Schwarz S, et al. PD1-positive tumor-infiltrating lymphocytes are associated with poor clinical outcome after pulmonary metastasectomy for colorectal cancer. Oncoimmunology 2017;6:e1331194. [Crossref] [PubMed]
7. Okada S, Itoh K, Ishihara S, et al. Significance of PD-L1 expression in pulmonary metastases from head and neck squamous cell carcinoma. Surg Oncol 2018;27:259-65. [Crossref] [PubMed]
8. Mansfield AS, Brown RJ, Sammon C, et al. The Predictive and Prognostic Nature of Programmed Death-Ligand 1 in Malignant Pleural Mesothelioma: A Systematic Literature Review. JTO Clin Res Rep 2022;3:100315. [Crossref] [PubMed]
9. Gazivoda VP, Kangas-Dick AW, Greenbaum AA, et al. Expression of PD-L1 in Patients With Malignant Peritoneal Mesothelioma: A Pilot Study. J Surg Res 2022;277:131-7. [Crossref] [PubMed]
10. Brcic L, Klikovits T, Megyesfalvi Z, et al. Prognostic impact of PD-1 and PD-L1 expression in malignant pleural mesothelioma: an international multicenter study. Transl Lung Cancer Res 2021;10:1594-607. [Crossref] [PubMed]
11. Okita R, Mimura-Kimura Y, Kawamoto N, et al. Effects of tumor-infiltrating CD8+ T cells, PD1/PD-L1 axis, and expression patterns of HLA class I on the prognosis of patients with malignant pleural mesothelioma who underwent extra-pleural pneumonectomy. Cancer Immunol Immunother 2023;72:865-79. [Crossref] [PubMed]
12. Lee HS, Hamaji M, Palivela N, et al. Prognostic Role of Programmed Cell Death 1 Ligand 1 in Resectable Pleural Mesothelioma. Ann Thorac Surg 2021;112:1575-83. [Crossref] [PubMed]
13. Hasegawa S, Shintani Y, Takuwa T, et al. Nationwide prospective registry database of patients with newly diagnosed untreated pleural mesothelioma in Japan. Cancer Sci 2024;115:507-28. [Crossref] [PubMed]
14. Kanayama M, Mori M, Matsumiya H, et al. Surgical strategy for malignant pleural mesothelioma: the superiority of pleurectomy/decortication. Surg Today 2022;52:1031-8. [Crossref] [PubMed]
15. Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982;5:649-55.
16. Tanaka F, Imanishi N, Takenaka M, et al. Non-incisional pleurectomy-decortication for malignant pleural mesothelioma. Surg Today 2018;48:656-8. [Crossref] [PubMed]
17. Hirai A, Yoneda K, Shimajiri S, et al. Prognostic impact of programmed death-ligand 1 expression in correlation with human leukocyte antigen class I expression status in stage I adenocarcinoma of the lung. J Thorac Cardiovasc Surg 2018;155:382-392.e1. [Crossref] [PubMed]
18. Tashima Y, Kuwata T, Yoneda K, et al. Prognostic impact of PD-L1 expression in correlation with neutrophil-to-lymphocyte ratio in squamous cell carcinoma of the lung. Sci Rep 2020;10:1243. [Crossref] [PubMed]
19. Brosseau S, Danel C, Scherpereel A, et al. Shorter Survival in Malignant Pleural Mesothelioma Patients With High PD-L1 Expression Associated With Sarcomatoid or Biphasic Histology Subtype: A Series of 214 Cases From the Bio-MAPS Cohort. Clin Lung Cancer 2019;20:e564-75. [Crossref] [PubMed]
20. Tanaka F, Takenaka M, Imanishi N, et al. Non-incisional pleurectomy/decortication for malignant pleural mesothelioma. Gen Thorac Cardiovasc Surg 2021;69:1320-5. [Crossref] [PubMed]
21. Patil NS, Righi L, Koeppen H, et al. Molecular and Histopathological Characterization of the Tumor Immune Microenvironment in Advanced Stage of Malignant Pleural Mesothelioma. J Thorac Oncol 2018;13:124-33. [Crossref] [PubMed]
22. Wolchok JD, Kluger H, Callahan MK, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 2013;369:122-33. [Crossref] [PubMed]
23. Reck M, Rodríguez-Abreu D, Robinson AG, et al. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med 2016;375:1823-33. [Crossref] [PubMed]
24. Schmid P, Adams S, Rugo HS, et al. Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer. N Engl J Med 2018;379:2108-21. [Crossref] [PubMed]
25. Chu Q, Perrone F, Greillier L, et al. Pembrolizumab plus chemotherapy versus chemotherapy in untreated advanced pleural mesothelioma in Canada, Italy, and France: a phase 3, open-label, randomised controlled trial. Lancet 2023;402:2295-306. [Crossref] [PubMed]
26. Reuss JE, Sepesi B, Rolfo CD, et al. Trial in progress: Neoadjuvant immune checkpoint blockade in resectable malignant pleural mesothelioma. J Clin Oncol 2020;38:TPS9078.
27. Offin M, Lavin Y, Zatzman M, et al. Feasibility and safety of neoadjuvant nivolumab and chemotherapy for resectable diffuse pleural mesotheliomas: Results of a prospective pilot study. J Clin Oncol 2024;42:8003.
28. Ma J, Li J, Qian M, et al. PD-L1 expression and the prognostic significance in gastric cancer: a retrospective comparison of three PD-L1 antibody clones (SP142, 28-8 and E1L3N). Diagn Pathol 2018;13:91. [Crossref] [PubMed]
29. Yamada N, Oizumi S, Kikuchi E, et al. CD8+ tumor-infiltrating lymphocytes predict favorable prognosis in malignant pleural mesothelioma after resection. Cancer Immunol Immunother 2010;59:1543-9. [Crossref] [PubMed]
30. Pasello G, Zago G, Lunardi F, et al. Malignant pleural mesothelioma immune microenvironment and checkpoint expression: correlation with clinical-pathological features and intratumor heterogeneity over time. Ann Oncol 2018;29:1258-65. [Crossref] [PubMed]
31. de Perrot M, Wu L, Cabanero M, et al. Prognostic influence of tumor microenvironment after hypofractionated radiation and surgery for mesothelioma. J Thorac Cardiovasc Surg 2020;159:2082-2091.e1. [Crossref] [PubMed]
32. Marabelle A, Fakih M, Lopez J, et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol 2020;21:1353-65. [Crossref] [PubMed]