Prognostic significance of tumor infiltrating lymphocytes on first-line pembrolizumab efficacy in advanced non-small cell lung cancer
Abstract Aim Tumor-infiltrating lymphocytes (TILs) in the tumor and stroma are expected to accurately predict the efficacy of programmed death-1 (PD-1) blockade therapy. However, little is known about the prognostic significance of TILs in first-line PD-1 therapy. We assessed TILs in patients with a...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer
2023-01-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-023-00615-4 |
| _version_ | 1797945801991782400 |
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| author | Kyoichi Kaira Ou Yamaguchi Tomonori Kawasaki Kousuke Hashimoto Yu Miura Ayako Shiono Atsuto Mouri Hisao Imai Kunihiko Kobayashi Masanori Yasuda Hiroshi Kagamu |
| author_facet | Kyoichi Kaira Ou Yamaguchi Tomonori Kawasaki Kousuke Hashimoto Yu Miura Ayako Shiono Atsuto Mouri Hisao Imai Kunihiko Kobayashi Masanori Yasuda Hiroshi Kagamu |
| author_sort | Kyoichi Kaira |
| collection | DOAJ |
| description | Abstract Aim Tumor-infiltrating lymphocytes (TILs) in the tumor and stroma are expected to accurately predict the efficacy of programmed death-1 (PD-1) blockade therapy. However, little is known about the prognostic significance of TILs in first-line PD-1 therapy. We assessed TILs in patients with advanced or metastatic non-small cell lung cancer (NSCLC) treated with pembrolizumab in the palliative setting. Methods Multiplex immunohistochemistry staining of TILs (CD4, CD8, Foxp3, and PD-1) and immunohistochemical staining of CK and PD-L1 in the tumor and stroma was performed in tumor specimens of 107 NSCLC patients and correlated with clinical outcomes, as a single-center retrospective study. TILs and programmed death ligand-1 (PD-L1) were assessed on biopsies (N = 93) or surgical resections (N = 14) before first-line pembrolizumab. Results A low number of stromal CD4 TILs were significantly associated with bone metastasis and poor performance status (PS). The median progression-free survival (PFS) and overall survival (OS) were significantly higher in patients with a high number of stromal CD4 TILs (336 days and 731 days, respectively) than in those with low infiltration (204 days and 333 days, respectively). Patients with a high number of intratumoral CD8 TILs (731 days) yielded significantly better OS than those with low infiltration (333 days), but not for PFS. Multivariate analysis confirmed that stromal CD4 TILs were independent predictors of PFS, but not OS. Furthermore, intratumoral CD8 TILs were independent predictors of better OS. In the survival analysis of key subgroups, stromal CD4 TILs were identified as significant predictors of survival in patients with non-adenocarcinomatous histology and PD-L1 ≥ 50%. Conclusion Stromal CD4 TILs were identified as a significant marker for predicting the PFS after pembrolizumab therapy, especially in patients with non-adenocarcinoma and high PD-L1 expression. In addition, intratumoral CD8 TILs were identified as significant predictors of OS. |
| first_indexed | 2024-04-10T21:00:52Z |
| format | Article |
| id | doaj.art-51df83129f1f4f2b811f207816e4829f |
| institution | Directory Open Access Journal |
| issn | 2730-6011 |
| language | English |
| last_indexed | 2024-04-10T21:00:52Z |
| publishDate | 2023-01-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj.art-51df83129f1f4f2b811f207816e4829f2023-01-22T12:17:51ZengSpringerDiscover Oncology2730-60112023-01-0114111310.1007/s12672-023-00615-4Prognostic significance of tumor infiltrating lymphocytes on first-line pembrolizumab efficacy in advanced non-small cell lung cancerKyoichi Kaira0Ou Yamaguchi1Tomonori Kawasaki2Kousuke Hashimoto3Yu Miura4Ayako Shiono5Atsuto Mouri6Hisao Imai7Kunihiko Kobayashi8Masanori Yasuda9Hiroshi Kagamu10Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical UniversityDepartment of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical UniversityDepartment of Pathology, International Medical Center, Saitama Medical UniversityDepartment of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical UniversityDepartment of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical UniversityDepartment of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical UniversityDepartment of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical UniversityDepartment of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical UniversityDepartment of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical UniversityDepartment of Pathology, International Medical Center, Saitama Medical UniversityDepartment of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical UniversityAbstract Aim Tumor-infiltrating lymphocytes (TILs) in the tumor and stroma are expected to accurately predict the efficacy of programmed death-1 (PD-1) blockade therapy. However, little is known about the prognostic significance of TILs in first-line PD-1 therapy. We assessed TILs in patients with advanced or metastatic non-small cell lung cancer (NSCLC) treated with pembrolizumab in the palliative setting. Methods Multiplex immunohistochemistry staining of TILs (CD4, CD8, Foxp3, and PD-1) and immunohistochemical staining of CK and PD-L1 in the tumor and stroma was performed in tumor specimens of 107 NSCLC patients and correlated with clinical outcomes, as a single-center retrospective study. TILs and programmed death ligand-1 (PD-L1) were assessed on biopsies (N = 93) or surgical resections (N = 14) before first-line pembrolizumab. Results A low number of stromal CD4 TILs were significantly associated with bone metastasis and poor performance status (PS). The median progression-free survival (PFS) and overall survival (OS) were significantly higher in patients with a high number of stromal CD4 TILs (336 days and 731 days, respectively) than in those with low infiltration (204 days and 333 days, respectively). Patients with a high number of intratumoral CD8 TILs (731 days) yielded significantly better OS than those with low infiltration (333 days), but not for PFS. Multivariate analysis confirmed that stromal CD4 TILs were independent predictors of PFS, but not OS. Furthermore, intratumoral CD8 TILs were independent predictors of better OS. In the survival analysis of key subgroups, stromal CD4 TILs were identified as significant predictors of survival in patients with non-adenocarcinomatous histology and PD-L1 ≥ 50%. Conclusion Stromal CD4 TILs were identified as a significant marker for predicting the PFS after pembrolizumab therapy, especially in patients with non-adenocarcinoma and high PD-L1 expression. In addition, intratumoral CD8 TILs were identified as significant predictors of OS.https://doi.org/10.1007/s12672-023-00615-4Tumor-infiltrating lymphocytesCD4CD8PD-1PD-L1Non-small cell lung cancer |
| spellingShingle | Kyoichi Kaira Ou Yamaguchi Tomonori Kawasaki Kousuke Hashimoto Yu Miura Ayako Shiono Atsuto Mouri Hisao Imai Kunihiko Kobayashi Masanori Yasuda Hiroshi Kagamu Prognostic significance of tumor infiltrating lymphocytes on first-line pembrolizumab efficacy in advanced non-small cell lung cancer Discover Oncology Tumor-infiltrating lymphocytes CD4 CD8 PD-1 PD-L1 Non-small cell lung cancer |
| title | Prognostic significance of tumor infiltrating lymphocytes on first-line pembrolizumab efficacy in advanced non-small cell lung cancer |
| title_full | Prognostic significance of tumor infiltrating lymphocytes on first-line pembrolizumab efficacy in advanced non-small cell lung cancer |
| title_fullStr | Prognostic significance of tumor infiltrating lymphocytes on first-line pembrolizumab efficacy in advanced non-small cell lung cancer |
| title_full_unstemmed | Prognostic significance of tumor infiltrating lymphocytes on first-line pembrolizumab efficacy in advanced non-small cell lung cancer |
| title_short | Prognostic significance of tumor infiltrating lymphocytes on first-line pembrolizumab efficacy in advanced non-small cell lung cancer |
| title_sort | prognostic significance of tumor infiltrating lymphocytes on first line pembrolizumab efficacy in advanced non small cell lung cancer |
| topic | Tumor-infiltrating lymphocytes CD4 CD8 PD-1 PD-L1 Non-small cell lung cancer |
| url | https://doi.org/10.1007/s12672-023-00615-4 |
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