ニボルマブ治療を行った口腔・咽頭癌の臨床病理学的検討
2017年9月から2019年7月までに埼玉医科大学国際医療センターでニボルマブを導入した口腔・咽頭癌症例の臨床病理学的因子と予後との関連を検討した．症例は口腔癌が8例，咽頭癌が20例で生存期間中央値は10ヵ月であった．ECOG PSが2以上，好中球リンパ球比（NLR）が5以上，血清CRP値が0.87mg/dl以上の症例は有意に予後不良であった（p＝0.0004，0.01，0.03）．初期病理検体のPD-L1発現，腫瘍浸潤リンパ球（CD4，CD8，FoxP3）は予後と関連しなかったが，腫瘍関連マクロファージ（CD163）の高発現群は予後不良の傾向が見られた．今後更なる予後予測因子の開発が望まれる...
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| Published in | 口腔・咽頭科 Vol. 36; no. 2; pp. 191 - 198 |
|---|---|
| Main Authors | , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
日本口腔・咽頭科学会
2023
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0917-5105 1884-4316 |
| DOI | 10.14821/stomatopharyngology.36.191 |
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| Abstract | 2017年9月から2019年7月までに埼玉医科大学国際医療センターでニボルマブを導入した口腔・咽頭癌症例の臨床病理学的因子と予後との関連を検討した．症例は口腔癌が8例，咽頭癌が20例で生存期間中央値は10ヵ月であった．ECOG PSが2以上，好中球リンパ球比（NLR）が5以上，血清CRP値が0.87mg/dl以上の症例は有意に予後不良であった（p＝0.0004，0.01，0.03）．初期病理検体のPD-L1発現，腫瘍浸潤リンパ球（CD4，CD8，FoxP3）は予後と関連しなかったが，腫瘍関連マクロファージ（CD163）の高発現群は予後不良の傾向が見られた．今後更なる予後予測因子の開発が望まれる． |
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| AbstractList | 2017年9月から2019年7月までに埼玉医科大学国際医療センターでニボルマブを導入した口腔・咽頭癌症例の臨床病理学的因子と予後との関連を検討した．症例は口腔癌が8例，咽頭癌が20例で生存期間中央値は10ヵ月であった．ECOG PSが2以上，好中球リンパ球比（NLR）が5以上，血清CRP値が0.87mg/dl以上の症例は有意に予後不良であった（p＝0.0004，0.01，0.03）．初期病理検体のPD-L1発現，腫瘍浸潤リンパ球（CD4，CD8，FoxP3）は予後と関連しなかったが，腫瘍関連マクロファージ（CD163）の高発現群は予後不良の傾向が見られた．今後更なる予後予測因子の開発が望まれる． |
| Author | 中平, 光彦 久場, 潔実 菅澤, 正 |
| Author_xml | – sequence: 1 fullname: 菅澤, 正 organization: 亀田総合病院頭頸部外科 – sequence: 1 fullname: 中平, 光彦 organization: 埼玉医科大学国際医療センター頭頸部腫瘍科・耳鼻咽喉科 – sequence: 1 fullname: 久場, 潔実 organization: 埼玉医科大学国際医療センター頭頸部腫瘍科・耳鼻咽喉科 |
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| References | 4） Li F, Li C, Cai X, et al: The association between CD8＋ tumor-infiltrating lymphocytes and the clinical outcome of cancer immunotherapy: A systematic review and meta-analysis. EClinicalMedicine 2021；41：101134. 9） 川瀨勝隆，越塚慶一，米田理葉，他：ニボルマブを使用した再発・転移性頭頸部癌44例の検討．頭頸部癌 2021；47：284-289. 13） Nakamura Y, Kitano S, Takahashi A, et al: Nivolumab for advanced melanoma: pretreatment prognostic factors and early outcome markers during therapy. Oncotarget 2016；7：77404-77415. 16） de Ruiter EJ, Ooft ML, Devriese LA, et al: The prognostic role of tumor infiltrating T-lymphocytes in squamous cell carcinoma of the head and neck: A systematic review and meta-analysis. Oncoimmunology 2017；6：e1356148. 12） Morita R, Okishio K, Shimizu J, et al: Real-world effectiveness and safety of nivolumab in patients with non-small cell lung cancer: a multicenter retrospective observational study in Japan. Lung Cancer 2020；140：8-18. 15） Hanai N, Shimizu Y, Kariya S, et al: Effectiveness and safety of nivolumab in patients with head and neck cancer in Japanese real-world clinical practice: a multicenter retrospective clinical study. Int J Clin Oncol 2020；26：494-506. 7） Matsuki T, Okamoto I, Fushimi C, et al: Hematological predictive markers for recurrent or metastatic squamous cell carcinomas of the head and neck treated with nivolumab: A multicenter study of 88 patients. Cancer Med 2020；9：5015-5024. 24） Troiano G, Caponio VA, Adipietro I, et al: Prognostic significance of CD68＋ and CD163＋ tumor associated macrophages in head and neck squamous cell carcinoma: A systematic review and meta-analysis. Oral Oncol 2019；93：66-75. 14） Singh P, McDonald L, Waldenberger D, et al: Pooled analysis of nivolumab treatment in patients with recurrent/metastatic squamous cell carcinoma of the head and neck in the United States and Germany. Head Neck 2021；43：3540-3551. 18） Hori S, Nomura T, Sakaguchi S: Control of regulatory T cell development by the transcription factor Foxp3. Science 2003；299：1057-1061. 19） Seminerio I, Descamps G, Dupont S, et al: Infiltration of FoxP3＋ Regulatory T Cells is a Strong and Independent Prognostic Factor in Head and Neck Squamous Cell Carcinoma. Cancers （Basel） 2019；11：227. 10） Chen Y, Cong R, Ji C, et al: The prognostic role of C-reactive protein in patients with head and neck squamous cell carcinoma: A meta-analysis. Cancer Med 2020；9：9541-9553. 22） Ock CY, Kim S, Keam B, et al: Changes in programmed death-ligand 1 expression during cisplatin treatment in patients with head and neck squamous cell carcinoma. Oncotarget 2017；8：97920-97927. 20） Cho JH, Lim YC: Prognostic impact of regulatory T cell in head and neck squamous cell carcinoma: A systematic review and meta-analysis. Oral Oncol 2021；112：105084. 6） Kanda Y: Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 2013；48：452-458. 23） Sumitomo R, Hirai T, Fujita M, et al: M2 tumor-associated macrophages promote tumor progression in non-small-cell lung cancer. Exp Ther Med 2019；18：4490-4498. 25） Gordon SR, Mautte RL, Dulken BW, et al: PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature 2017；545：495-499. 1） Burtness B, Harrington KJ, Greil R, et al: Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck （KEYNOTE-048）: A randomized, open-label, phase 3 study. LANCET 2019；394：1915-1928. 17） Borsetto D, Tomasoni M, Payne K, et al: Prognostic significance of CD4＋ and CD8＋ tumor-infiltrating lymphocytes in head and neck squamous cell carcinoma: A meta-analysis. Cancers （Basel） 2021；13：781. 5） Takahashi H, Sakakura K, Kudo T, et al: Cancer-associated fibroblasts promote an immunosuppressive microenvironment through the induction and accumulation of protumoral macrophages. Oncotarget 2017；8：8633-8647. 26） Fujimura T, Sato Y, Tanita K, et al: Serum Level of Soluble CD163 May Be a Predictive Marker of the Effectiveness of Nivolumab in Patients With Advanced Cutaneous Melanoma. Front Oncol 2018；8：530. 11） Ueki Y, Takahashi T, Ota H, et al: Predicting the treatment outcome of nivolumab in recurrent or metastatic head and neck squamous cell carcinoma: prognostic value of combined performance status and modified Glasgow prognostic score. Eur Arch Otorhinolaryngol 2020；277：2341-2347. 3） Oliva M, Spreafico A, Taberna M, et al: Immune biomarkers of response to immune-checkpoint inhibitors in head and neck squamous cell carcinoma. Ann Oncol 2019；30：57-67. 8） Ueda T, Chikuie N, Takumida M, et al: Baseline neutrophil-to-lymphocyte ratio （NLR） is associated with clinical outcome in recurrent or metastatic head and neck cancer patients treated with nivolumab. Clin Transl Oncol 2020；22：1818-1824. 21）Ahn S, Chung YR, Seo AN, et al: Changes and prognostic values of tumor-infiltrating lymphocyte subsets after primary systemic therapy in breast cancer. PloS One 2020；15：e0233037. 2） Huang Z, Zheng S, Ding S, et al: Prognostic role of programmed cell death ligand-1 expression in head and neck cancer treated with programmed cell death protein-1/programmed cell death ligand-1 inhibitors: A meta-analysis based on clinical trials. J Cancer Res Ther 2021；17：676-687. |
| References_xml | – reference: 5） Takahashi H, Sakakura K, Kudo T, et al: Cancer-associated fibroblasts promote an immunosuppressive microenvironment through the induction and accumulation of protumoral macrophages. Oncotarget 2017；8：8633-8647. – reference: 1） Burtness B, Harrington KJ, Greil R, et al: Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck （KEYNOTE-048）: A randomized, open-label, phase 3 study. LANCET 2019；394：1915-1928. – reference: 19） Seminerio I, Descamps G, Dupont S, et al: Infiltration of FoxP3＋ Regulatory T Cells is a Strong and Independent Prognostic Factor in Head and Neck Squamous Cell Carcinoma. Cancers （Basel） 2019；11：227. – reference: 6） Kanda Y: Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 2013；48：452-458. – reference: 15） Hanai N, Shimizu Y, Kariya S, et al: Effectiveness and safety of nivolumab in patients with head and neck cancer in Japanese real-world clinical practice: a multicenter retrospective clinical study. Int J Clin Oncol 2020；26：494-506. – reference: 18） Hori S, Nomura T, Sakaguchi S: Control of regulatory T cell development by the transcription factor Foxp3. Science 2003；299：1057-1061. – reference: 13） Nakamura Y, Kitano S, Takahashi A, et al: Nivolumab for advanced melanoma: pretreatment prognostic factors and early outcome markers during therapy. Oncotarget 2016；7：77404-77415. – reference: 9） 川瀨勝隆，越塚慶一，米田理葉，他：ニボルマブを使用した再発・転移性頭頸部癌44例の検討．頭頸部癌 2021；47：284-289. – reference: 26） Fujimura T, Sato Y, Tanita K, et al: Serum Level of Soluble CD163 May Be a Predictive Marker of the Effectiveness of Nivolumab in Patients With Advanced Cutaneous Melanoma. Front Oncol 2018；8：530. – reference: 23） Sumitomo R, Hirai T, Fujita M, et al: M2 tumor-associated macrophages promote tumor progression in non-small-cell lung cancer. Exp Ther Med 2019；18：4490-4498. – reference: 22） Ock CY, Kim S, Keam B, et al: Changes in programmed death-ligand 1 expression during cisplatin treatment in patients with head and neck squamous cell carcinoma. Oncotarget 2017；8：97920-97927. – reference: 10） Chen Y, Cong R, Ji C, et al: The prognostic role of C-reactive protein in patients with head and neck squamous cell carcinoma: A meta-analysis. Cancer Med 2020；9：9541-9553. – reference: 17） Borsetto D, Tomasoni M, Payne K, et al: Prognostic significance of CD4＋ and CD8＋ tumor-infiltrating lymphocytes in head and neck squamous cell carcinoma: A meta-analysis. Cancers （Basel） 2021；13：781. – reference: 20） Cho JH, Lim YC: Prognostic impact of regulatory T cell in head and neck squamous cell carcinoma: A systematic review and meta-analysis. Oral Oncol 2021；112：105084. – reference: 14） Singh P, McDonald L, Waldenberger D, et al: Pooled analysis of nivolumab treatment in patients with recurrent/metastatic squamous cell carcinoma of the head and neck in the United States and Germany. Head Neck 2021；43：3540-3551. – reference: 21）Ahn S, Chung YR, Seo AN, et al: Changes and prognostic values of tumor-infiltrating lymphocyte subsets after primary systemic therapy in breast cancer. PloS One 2020；15：e0233037. – reference: 7） Matsuki T, Okamoto I, Fushimi C, et al: Hematological predictive markers for recurrent or metastatic squamous cell carcinomas of the head and neck treated with nivolumab: A multicenter study of 88 patients. Cancer Med 2020；9：5015-5024. – reference: 11） Ueki Y, Takahashi T, Ota H, et al: Predicting the treatment outcome of nivolumab in recurrent or metastatic head and neck squamous cell carcinoma: prognostic value of combined performance status and modified Glasgow prognostic score. Eur Arch Otorhinolaryngol 2020；277：2341-2347. – reference: 12） Morita R, Okishio K, Shimizu J, et al: Real-world effectiveness and safety of nivolumab in patients with non-small cell lung cancer: a multicenter retrospective observational study in Japan. Lung Cancer 2020；140：8-18. – reference: 16） de Ruiter EJ, Ooft ML, Devriese LA, et al: The prognostic role of tumor infiltrating T-lymphocytes in squamous cell carcinoma of the head and neck: A systematic review and meta-analysis. Oncoimmunology 2017；6：e1356148. – reference: 4） Li F, Li C, Cai X, et al: The association between CD8＋ tumor-infiltrating lymphocytes and the clinical outcome of cancer immunotherapy: A systematic review and meta-analysis. EClinicalMedicine 2021；41：101134. – reference: 3） Oliva M, Spreafico A, Taberna M, et al: Immune biomarkers of response to immune-checkpoint inhibitors in head and neck squamous cell carcinoma. Ann Oncol 2019；30：57-67. – reference: 25） Gordon SR, Mautte RL, Dulken BW, et al: PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature 2017；545：495-499. – reference: 2） Huang Z, Zheng S, Ding S, et al: Prognostic role of programmed cell death ligand-1 expression in head and neck cancer treated with programmed cell death protein-1/programmed cell death ligand-1 inhibitors: A meta-analysis based on clinical trials. J Cancer Res Ther 2021；17：676-687. – reference: 8） Ueda T, Chikuie N, Takumida M, et al: Baseline neutrophil-to-lymphocyte ratio （NLR） is associated with clinical outcome in recurrent or metastatic head and neck cancer patients treated with nivolumab. Clin Transl Oncol 2020；22：1818-1824. – reference: 24） Troiano G, Caponio VA, Adipietro I, et al: Prognostic significance of CD68＋ and CD163＋ tumor associated macrophages in head and neck squamous cell carcinoma: A systematic review and meta-analysis. Oral Oncol 2019；93：66-75. |
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| SubjectTerms | ニボルマブ 口腔癌 咽頭癌 頭頸部癌 |
| Title | ニボルマブ治療を行った口腔・咽頭癌の臨床病理学的検討 |
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