Skip to main content
Erschienen in: Cancer Immunology, Immunotherapy 10/2020

24.05.2020 | Original Article

PD-L1 expression correlates with tumor-infiltrating lymphocytes and better prognosis in patients with HPV-negative head and neck squamous cell carcinomas

verfasst von: Mario Sanchez-Canteli, Rocio Granda-Díaz, Nagore del Rio-Ibisate, Eva Allonca, Fernando López-Alvarez, Jackeline Agorreta, Irati Garmendia, Luis M. Montuenga, Juana M. García-Pedrero, Juan P. Rodrigo

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 10/2020

Einloggen, um Zugang zu erhalten

Abstract

Introduction

The importance of immune tumor microenvironment in the prognosis of patients with head and neck squamous carcinomas (HNSCC) is increasingly recognized. We analyzed the prognostic relevance of PD-L1 and PD-1 expressions in relation to the infiltration by CD8+ and FOXP3+ tumor-infiltrating lymphocytes (TILs).

Methods

Samples from 372 surgically treated HPV-negative HNSCC patients were evaluated by immunohistochemistry for PD-L1 expression [both tumor proportion score (TPS) and combined proportion score (CPS)], PD-1 expression in immune cells, and density of infiltrating CD8+ and FOXP3+ TILs. PD-L1 expression and CD8+ TIL density were combined to establish the type of tumor microenvironment.

Results

29.5% cases exhibited PD-L1 TPS positivity (≥ 1%), whereas PD-L1 CPS positivity (≥ 1%) was observed in 40% cases. 47.5% cases showed positive PD-1 expression (≥ 1%). PD-L1 and PD-1 positivity correlated with a high density of both CD8+ and FOXP3+ TILs. In univariate analysis, PD-L1 TPS positivity (P = 0.026), PD-L1 CPS positivity (P = 0.004), high density of CD8+ TIL (P = 0.001), and high density of FOXP3+ TIL (P = 0.004) were associated with a better disease-specific survival (DSS). However, in multivariate analysis, only high density of CD8+ TIL was associated with a better DSS (P = 0.002). The type of tumor microenvironment correlated with DSS (P = .008), with the better DSS observed in cases with type I (PD-L1 CPS positivity and high density of CD8+ TIL).

Conclusions

High infiltration by CD8+ TIL is associated with better survival outcomes. Positive PD-L1 expression correlates with a high infiltration by TILs, explaining its association with better prognosis.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
5.
Zurück zum Zitat Cohen EEW, Bell RB, Bifulco CB, Burtness B, Gillison ML, Harrington KJ, Le QT, Lee NY, Leidner R, Lewis RL, Licitra L, Mehanna H, Mell LK, Raben A, Sikora AG, Uppaluri R, Whitworth F, Zandberg DP, Ferris RL (2019) The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC). J Immunother Cancer 7:184. https://doi.org/10.1186/s40425-019-0662-5CrossRefPubMedPubMedCentral Cohen EEW, Bell RB, Bifulco CB, Burtness B, Gillison ML, Harrington KJ, Le QT, Lee NY, Leidner R, Lewis RL, Licitra L, Mehanna H, Mell LK, Raben A, Sikora AG, Uppaluri R, Whitworth F, Zandberg DP, Ferris RL (2019) The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC). J Immunother Cancer 7:184. https://​doi.​org/​10.​1186/​s40425-019-0662-5CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Carbognin L, Pilotto S, Milella M, Vaccaro V, Brunelli M, Caliò A, Cuppone F, Sperduti I, Giannarelli D, Chilosi M, Bronte V, Scarpa A, Bria E, Tortora G (2015) Differential activity of Nivolumab, Pembrolizumab and MPDL3280A according to the tumor expression of programmed death-Ligand-1 (PD-L1): sensitivity analysis of trials in melanoma, lung and genitourinary cancers. PLoS ONE 10:e0130142. https://doi.org/10.1371/journal.pone.0130142CrossRefPubMedPubMedCentral Carbognin L, Pilotto S, Milella M, Vaccaro V, Brunelli M, Caliò A, Cuppone F, Sperduti I, Giannarelli D, Chilosi M, Bronte V, Scarpa A, Bria E, Tortora G (2015) Differential activity of Nivolumab, Pembrolizumab and MPDL3280A according to the tumor expression of programmed death-Ligand-1 (PD-L1): sensitivity analysis of trials in melanoma, lung and genitourinary cancers. PLoS ONE 10:e0130142. https://​doi.​org/​10.​1371/​journal.​pone.​0130142CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Mehra R, Seiwert TY, Gupta S, Weiss J, Gluck I, Eder JP, Burtness B, Tahara M, Keam B, Kang H, Muro K, Geva R, Chung HC, Lin CC, Aurora-Garg D, Ray A, Pathiraja K, Cheng J, Chow LQM, Haddad R (2018) Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: pooled analyses after long-term follow-up in KEYNOTE-012. Br J Cancer 119:153–159. https://doi.org/10.1038/s41416-018-0131-9CrossRefPubMedPubMedCentral Mehra R, Seiwert TY, Gupta S, Weiss J, Gluck I, Eder JP, Burtness B, Tahara M, Keam B, Kang H, Muro K, Geva R, Chung HC, Lin CC, Aurora-Garg D, Ray A, Pathiraja K, Cheng J, Chow LQM, Haddad R (2018) Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: pooled analyses after long-term follow-up in KEYNOTE-012. Br J Cancer 119:153–159. https://​doi.​org/​10.​1038/​s41416-018-0131-9CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington KJ, Kasper S, Vokes EE, Even C, Worden F, Saba NF, Docampo LCI, Haddad R, Rordorf T, Kiyota N, Tahara M, Lynch M, Jayaprakash V, Li L, Gillison ML (2018) Nivolumab vs investigator’s choice in recurrent or metastatic squamous cell carcinoma of the head and neck: 2-year long-term survival update of CheckMate 141 with analyses by tumor PD-L1 expression. Oral Oncol 81:45–51. https://doi.org/10.1016/j.oraloncology.2018.04.008CrossRefPubMedPubMedCentral Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington KJ, Kasper S, Vokes EE, Even C, Worden F, Saba NF, Docampo LCI, Haddad R, Rordorf T, Kiyota N, Tahara M, Lynch M, Jayaprakash V, Li L, Gillison ML (2018) Nivolumab vs investigator’s choice in recurrent or metastatic squamous cell carcinoma of the head and neck: 2-year long-term survival update of CheckMate 141 with analyses by tumor PD-L1 expression. Oral Oncol 81:45–51. https://​doi.​org/​10.​1016/​j.​oraloncology.​2018.​04.​008CrossRefPubMedPubMedCentral
12.
18.
Zurück zum Zitat Schneider S, Kadletz L, Wiebringhaus R, Kenner L, Selzer E, Füreder T, Rajky O, Berghoff AS, Preusser M, Heiduschka G (2018) PD-1 and PD-L1 expression in HNSCC primary cancer and related lymph node metastasis—impact on clinical outcome. Histopathology 73:573–584. https://doi.org/10.1111/his.13646CrossRefPubMed Schneider S, Kadletz L, Wiebringhaus R, Kenner L, Selzer E, Füreder T, Rajky O, Berghoff AS, Preusser M, Heiduschka G (2018) PD-1 and PD-L1 expression in HNSCC primary cancer and related lymph node metastasis—impact on clinical outcome. Histopathology 73:573–584. https://​doi.​org/​10.​1111/​his.​13646CrossRefPubMed
19.
Zurück zum Zitat Balermpas P, Rödel F, Krause M, Linge A, Lohaus F, Baumann M, Tinhofer I, Budach V, Sak A, Stuschke M, Gkika E, Grosu AL, Abdollahi A, Debus J, Stangl S, Ganswindt U, Belka C, Pigorsch S, Multhoff G, Combs SE, Welz S, Zips D, Lim SY, Rödel C, Fokas E, DKTK-ROG (2017) The PD-1/PD-L1 axis and human papilloma virus in patients with head and neck cancer after adjuvant chemoradiotherapy: a multicentre study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG). Int J Cancer 141:594–603. https://doi.org/10.1002/ijc.30770CrossRefPubMed Balermpas P, Rödel F, Krause M, Linge A, Lohaus F, Baumann M, Tinhofer I, Budach V, Sak A, Stuschke M, Gkika E, Grosu AL, Abdollahi A, Debus J, Stangl S, Ganswindt U, Belka C, Pigorsch S, Multhoff G, Combs SE, Welz S, Zips D, Lim SY, Rödel C, Fokas E, DKTK-ROG (2017) The PD-1/PD-L1 axis and human papilloma virus in patients with head and neck cancer after adjuvant chemoradiotherapy: a multicentre study of the German Cancer Consortium Radiation Oncology Group (DKTK-ROG). Int J Cancer 141:594–603. https://​doi.​org/​10.​1002/​ijc.​30770CrossRefPubMed
22.
Zurück zum Zitat Lipson EJ, Vincent JG, Loyo M, Kagohara LT, Luber BS, Wang H, Xu H, Nayar SK, Wang TS, Sidransky D, Anders RA, Topalian SL, Taube JM (2013) PD-L1 expression in the Merkel cell carcinoma microenvironment: association with inflammation, Merkel cell polyomavirus and overall survival. Cancer Immunol Res 1:54–63. https://doi.org/10.1158/2326-6066.CIR-13-0034CrossRefPubMed Lipson EJ, Vincent JG, Loyo M, Kagohara LT, Luber BS, Wang H, Xu H, Nayar SK, Wang TS, Sidransky D, Anders RA, Topalian SL, Taube JM (2013) PD-L1 expression in the Merkel cell carcinoma microenvironment: association with inflammation, Merkel cell polyomavirus and overall survival. Cancer Immunol Res 1:54–63. https://​doi.​org/​10.​1158/​2326-6066.​CIR-13-0034CrossRefPubMed
23.
Zurück zum Zitat Vilain RE, Menzies AM, Wilmott JS, Kakavand H, Madore J, Guminski A, Liniker E, Kong BY, Cooper AJ, Howle JR, Saw RPM, Jakrot V, Lo S, Thompson JF, Carlino MS, Kefford RF, Long GV, Scolyer RA (2017) Dynamic changes in PD-L1 expression and immune infiltrates early during treatment predict response to PD-1 blockade in Melanoma. Clin Cancer Res 23:5024–5033. https://doi.org/10.1158/1078-0432.CCR-16-0698CrossRefPubMed Vilain RE, Menzies AM, Wilmott JS, Kakavand H, Madore J, Guminski A, Liniker E, Kong BY, Cooper AJ, Howle JR, Saw RPM, Jakrot V, Lo S, Thompson JF, Carlino MS, Kefford RF, Long GV, Scolyer RA (2017) Dynamic changes in PD-L1 expression and immune infiltrates early during treatment predict response to PD-1 blockade in Melanoma. Clin Cancer Res 23:5024–5033. https://​doi.​org/​10.​1158/​1078-0432.​CCR-16-0698CrossRefPubMed
25.
Zurück zum Zitat Parra ER, Behrens C, Rodriguez-Canales J, Lin H, Mino B, Blando J, Zhang J, Gibbons DL, Heymach JV, Sepesi B, Swisher SG, Weissferdt A, Kalhor N, Izzo J, Kadara H, Moran C, Lee JJ, Wistuba II (2016) Image analysis-based assessment of PD-L1 and tumor-associated immune cells density supports distinct intratumoral microenvironment groups in non-small cell lung carcinoma patients. Clin Cancer Res 22:6278–6289. https://doi.org/10.1158/1078-0432.CCR-15-2443CrossRefPubMedPubMedCentral Parra ER, Behrens C, Rodriguez-Canales J, Lin H, Mino B, Blando J, Zhang J, Gibbons DL, Heymach JV, Sepesi B, Swisher SG, Weissferdt A, Kalhor N, Izzo J, Kadara H, Moran C, Lee JJ, Wistuba II (2016) Image analysis-based assessment of PD-L1 and tumor-associated immune cells density supports distinct intratumoral microenvironment groups in non-small cell lung carcinoma patients. Clin Cancer Res 22:6278–6289. https://​doi.​org/​10.​1158/​1078-0432.​CCR-15-2443CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Park K, Cho KJ, Lee M, Yoon DH, Kim SB (2013) Importance of FOXP3 in prognosis and its relationship with p16 in tonsillar squamous cell carcinoma. Anticancer Res 33:5667–5673PubMed Park K, Cho KJ, Lee M, Yoon DH, Kim SB (2013) Importance of FOXP3 in prognosis and its relationship with p16 in tonsillar squamous cell carcinoma. Anticancer Res 33:5667–5673PubMed
34.
Zurück zum Zitat Badoual C, Hans S, Merillon N, Van Ryswick C, Ravel P, Benhamouda N, Levionnois E, Nizard M, Si-Mohamed A, Besnier N, Gey A, Rotem-Yehudar R, Pere H, Tran T, Guerin CL, Chauvat A, Dransart E, Alanio C, Albert S, Barry B, Sandoval F, Quintin-Colonna F, Bruneval P, Fridman WH, Lemoine FM, Oudard S, Johannes L, Olive D, Brasnu D, Tartour E (2013) PD-1-expressing tumor-infiltrating T cells are a favorable prognostic biomarker in HPV-associated head and neck cancer. Cancer Res 73:128–138. https://doi.org/10.1158/0008-5472.CAN-12-2606CrossRefPubMed Badoual C, Hans S, Merillon N, Van Ryswick C, Ravel P, Benhamouda N, Levionnois E, Nizard M, Si-Mohamed A, Besnier N, Gey A, Rotem-Yehudar R, Pere H, Tran T, Guerin CL, Chauvat A, Dransart E, Alanio C, Albert S, Barry B, Sandoval F, Quintin-Colonna F, Bruneval P, Fridman WH, Lemoine FM, Oudard S, Johannes L, Olive D, Brasnu D, Tartour E (2013) PD-1-expressing tumor-infiltrating T cells are a favorable prognostic biomarker in HPV-associated head and neck cancer. Cancer Res 73:128–138. https://​doi.​org/​10.​1158/​0008-5472.​CAN-12-2606CrossRefPubMed
Metadaten
Titel
PD-L1 expression correlates with tumor-infiltrating lymphocytes and better prognosis in patients with HPV-negative head and neck squamous cell carcinomas
verfasst von
Mario Sanchez-Canteli
Rocio Granda-Díaz
Nagore del Rio-Ibisate
Eva Allonca
Fernando López-Alvarez
Jackeline Agorreta
Irati Garmendia
Luis M. Montuenga
Juana M. García-Pedrero
Juan P. Rodrigo
Publikationsdatum
24.05.2020
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Immunology, Immunotherapy / Ausgabe 10/2020
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-020-02604-w

Weitere Artikel der Ausgabe 10/2020

Cancer Immunology, Immunotherapy 10/2020 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.