Skip to main content
Erschienen in: Cancer Immunology, Immunotherapy 10/2017

27.05.2017 | Original Article

CD45RAFoxp3high regulatory T cells have a negative impact on the clinical outcome of head and neck squamous cell carcinoma

verfasst von: Fumie Ihara, Daiju Sakurai, Atsushi Horinaka, Yuji Makita, Akira Fujikawa, Toshioki Sakurai, Kazuki Yamasaki, Naoki Kunii, Shinichiro Motohashi, Toshinori Nakayama, Yoshitaka Okamoto

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 10/2017

Einloggen, um Zugang zu erhalten

Abstract

Background

Although regulatory T cells (Tregs) are thought to play an important role in immune suppression, their clinical significance in head and neck squamous cell carcinoma (HNSCC) is unclear. A recent study reported Tregs could be divided into functional subsets based on the expression of CD45RA and Foxp3.

Method

The frequency of circulating Treg subsets was analyzed in patients with HNSCC and compared with the frequency in patients with benign tumors. The association of Treg subsets with the frequency of lymphocyte subsets, status of progression, clinical course, and prognosis were also examined.

Results

The frequency of CD4+Foxp3+ Tregs was comparable between HNSCC patients and age-matched benign tumor patients; however, CD45RAFoxp3high Tregs were significantly increased in HNSCC patients, in particular those with advanced stage tumors. The high frequency of CD45RAFoxp3high Tregs correlated with a poor prognosis and the low frequency of CD45RAFoxp3high Tregs before treatment showed a better clinical outcome, even in patients with advanced stage tumors. CD45RAFoxp3high Treg numbers were decreased after intensive treatments; however, Treg numbers recovered in the early stages of recurrent cases, even before the clinical manifestation.

Conclusion

CD45RAFoxp3high Tregs are associated with the clinical course of HNSCC and might be a new target for treatment and an early marker of tumor recurrence in HNSCC patients.
Literatur
2.
Zurück zum Zitat Weed DT, Vella JL, Reis IM et al (2015) Tadalafil reduces myeloid-derived suppressor cells and regulatory T cells and promotes tumor immunity in patients with head and neck squamous cell carcinoma. Clin Cancer Res 21:39–48. doi:10.1158/1078-0432.CCR-14-1711 CrossRefPubMed Weed DT, Vella JL, Reis IM et al (2015) Tadalafil reduces myeloid-derived suppressor cells and regulatory T cells and promotes tumor immunity in patients with head and neck squamous cell carcinoma. Clin Cancer Res 21:39–48. doi:10.​1158/​1078-0432.​CCR-14-1711 CrossRefPubMed
6.
Zurück zum Zitat Horinaka A, Sakurai D, Ihara F, Makita Y, Kunii N, Motohashi S, Nakayama T, Okamoto Y (2016) Invariant NKT cells are resistant to circulating CD15+ myeloid-derived suppressor cells in patients with head and neck cancer. Cancer Sci. 107:207–216. doi:10.1111/cas.12866 CrossRef Horinaka A, Sakurai D, Ihara F, Makita Y, Kunii N, Motohashi S, Nakayama T, Okamoto Y (2016) Invariant NKT cells are resistant to circulating CD15+ myeloid-derived suppressor cells in patients with head and neck cancer. Cancer Sci. 107:207–216. doi:10.​1111/​cas.​12866 CrossRef
11.
Zurück zum Zitat Fujiwara J, Sowa Y, Horinaka M, Koyama M, Wakada M, Miki T, Sakai T (2016) The anti-obesity drug orlistat promotes sensitivity to TRAIL by two different pathways in hormone-refractory prostate cancer cells. Int J Oncol 48:854. doi:10.3892/ijo.2015.3265 CrossRefPubMed Fujiwara J, Sowa Y, Horinaka M, Koyama M, Wakada M, Miki T, Sakai T (2016) The anti-obesity drug orlistat promotes sensitivity to TRAIL by two different pathways in hormone-refractory prostate cancer cells. Int J Oncol 48:854. doi:10.​3892/​ijo.​2015.​3265 CrossRefPubMed
20.
Zurück zum Zitat Okita R, Saeki T, Takashima S, Yamaguchi Y, Toge T (2005) CD4+ CD25+ regulatory T cells in the peripheral blood of patients with breast cancer and non-small cell lung cancer. Oncol Rep 14:1269–1273PubMed Okita R, Saeki T, Takashima S, Yamaguchi Y, Toge T (2005) CD4+ CD25+ regulatory T cells in the peripheral blood of patients with breast cancer and non-small cell lung cancer. Oncol Rep 14:1269–1273PubMed
21.
Zurück zum Zitat Kono K, Kawaida H, Takahashi A, Sugai H, Mimura K, Miyagawa N, Omata H, Fujii H (2006) CD4(+)CD25high regulatory T cells increase with tumor stage in patients with gastric and esophageal cancers. Cancer Immunol Immunother 55:1064–1071. doi:10.1007/s00262-005-0092-8 CrossRefPubMed Kono K, Kawaida H, Takahashi A, Sugai H, Mimura K, Miyagawa N, Omata H, Fujii H (2006) CD4(+)CD25high regulatory T cells increase with tumor stage in patients with gastric and esophageal cancers. Cancer Immunol Immunother 55:1064–1071. doi:10.​1007/​s00262-005-0092-8 CrossRefPubMed
23.
Zurück zum Zitat Alhamarneh O, Agada F, Madden L, Stafford N, Greenman J (2011) Serum IL10 and circulating CD4(+) CD25(high) regulatory T cell numbers as predictors of clinical outcome and survival in patients with head and neck squamous cell carcinoma. Head Neck 33:415–423. doi:10.1002/hed.21464 PubMed Alhamarneh O, Agada F, Madden L, Stafford N, Greenman J (2011) Serum IL10 and circulating CD4(+) CD25(high) regulatory T cell numbers as predictors of clinical outcome and survival in patients with head and neck squamous cell carcinoma. Head Neck 33:415–423. doi:10.​1002/​hed.​21464 PubMed
25.
Zurück zum Zitat Salama P, Phillips M, Grieu F, Morris M, Zeps N, Joseph D, Platell C, Iacopetta B (2009) Tumor-infiltrating FOXP3+ T regulatory cells show strong prognostic significance in colorectal cancer. J Clin Oncol 27:186–192. doi:10.1200/JCO.2008.18.7229 CrossRefPubMed Salama P, Phillips M, Grieu F, Morris M, Zeps N, Joseph D, Platell C, Iacopetta B (2009) Tumor-infiltrating FOXP3+ T regulatory cells show strong prognostic significance in colorectal cancer. J Clin Oncol 27:186–192. doi:10.​1200/​JCO.​2008.​18.​7229 CrossRefPubMed
28.
Zurück zum Zitat Lin YC, Mahalingam J, Chiang JM et al (2013) Activated but not resting regulatory T cells accumulated in tumor microenvironment and correlated with tumor progression in patients with colorectal cancer. Inter J Cancer 132:1341–1350. doi:10.1002/ijc.27784 CrossRef Lin YC, Mahalingam J, Chiang JM et al (2013) Activated but not resting regulatory T cells accumulated in tumor microenvironment and correlated with tumor progression in patients with colorectal cancer. Inter J Cancer 132:1341–1350. doi:10.​1002/​ijc.​27784 CrossRef
30.
Zurück zum Zitat Yamaguchi T, Kishi A, Osaki M, Morikawa H, Prieto-Martin P, Wing K, Saito T, Sakaguchi S (2013) Construction of self-recognizing regulatory T cells from conventional T cells by controlling CTLA-4 and IL-2 expression. Proc Natl Acad Sci USA 110:E2116–E2125. doi:10.1073/pnas.1307185110 CrossRefPubMedPubMedCentral Yamaguchi T, Kishi A, Osaki M, Morikawa H, Prieto-Martin P, Wing K, Saito T, Sakaguchi S (2013) Construction of self-recognizing regulatory T cells from conventional T cells by controlling CTLA-4 and IL-2 expression. Proc Natl Acad Sci USA 110:E2116–E2125. doi:10.​1073/​pnas.​1307185110 CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Jafarzadeh A, Fooladseresht H, Minaee K, Bazrafshani MR, Khosravimashizi A, Nemati M, Mohammadizadeh M, Mohammadi MM, Ghaderi A (2015) Higher circulating levels of chemokine CCL22 in patients with breast cancer: evaluation of the influences of tumor stage and chemokine gene polymorphism. Tumour Biol 36:1163–1171. doi:10.1007/s13277-014-2739-6 CrossRefPubMed Jafarzadeh A, Fooladseresht H, Minaee K, Bazrafshani MR, Khosravimashizi A, Nemati M, Mohammadizadeh M, Mohammadi MM, Ghaderi A (2015) Higher circulating levels of chemokine CCL22 in patients with breast cancer: evaluation of the influences of tumor stage and chemokine gene polymorphism. Tumour Biol 36:1163–1171. doi:10.​1007/​s13277-014-2739-6 CrossRefPubMed
35.
Zurück zum Zitat Zhou G, Levitsky HI (2007) Natural regulatory T cells and de novo-induced regulatory T cells contribute independently to tumor-specific tolerance. J Immunology 178:2155–2162CrossRef Zhou G, Levitsky HI (2007) Natural regulatory T cells and de novo-induced regulatory T cells contribute independently to tumor-specific tolerance. J Immunology 178:2155–2162CrossRef
36.
Zurück zum Zitat Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, McGrady G, Wahl SM (2003) Conversion of peripheral CD4+ CD25− naive T cells to CD4+ CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 198:1875–1886. doi:10.1084/jem.20030152 CrossRefPubMedPubMedCentral Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, McGrady G, Wahl SM (2003) Conversion of peripheral CD4+ CD25 naive T cells to CD4+ CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 198:1875–1886. doi:10.​1084/​jem.​20030152 CrossRefPubMedPubMedCentral
37.
Zurück zum Zitat Liu VC, Wong LY, Jang T et al (2007) Tumor evasion of the immune system by converting CD4+ CD25− T cells into CD4+ CD25+ T regulatory cells: role of tumor-derived TGF-beta. J Immunology 178:2883–2892CrossRef Liu VC, Wong LY, Jang T et al (2007) Tumor evasion of the immune system by converting CD4+ CD25 T cells into CD4+ CD25+ T regulatory cells: role of tumor-derived TGF-beta. J Immunology 178:2883–2892CrossRef
Metadaten
Titel
CD45RA−Foxp3high regulatory T cells have a negative impact on the clinical outcome of head and neck squamous cell carcinoma
verfasst von
Fumie Ihara
Daiju Sakurai
Atsushi Horinaka
Yuji Makita
Akira Fujikawa
Toshioki Sakurai
Kazuki Yamasaki
Naoki Kunii
Shinichiro Motohashi
Toshinori Nakayama
Yoshitaka Okamoto
Publikationsdatum
27.05.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Immunology, Immunotherapy / Ausgabe 10/2017
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-017-2021-z

Weitere Artikel der Ausgabe 10/2017

Cancer Immunology, Immunotherapy 10/2017 Zur Ausgabe

Bessere Prognose mit links- statt rechtsseitigem Kolon-Ca.

06.05.2024 Kolonkarzinom Nachrichten

Menschen mit linksseitigem Kolonkarzinom leben im Mittel zweieinhalb Jahre länger als solche mit rechtsseitigem Tumor. Auch aktuell ist das Sterberisiko bei linksseitigen Tumoren US-Daten zufolge etwa um 11% geringer als bei rechtsseitigen.

Nodal-negativ nach neoadjuvanter Chemo: Axilladissektion verzichtbar?

03.05.2024 Mammakarzinom Nachrichten

Wenn bei Mammakarzinomen durch eine neoadjuvante Chemotherapie ein Downstaging von nodal-positiv zu nodal-negativ gelingt, scheint es auch ohne Axilladissektion nur selten zu axillären Rezidiven zu kommen.

Wo hapert es noch bei der Umsetzung der POMGAT-Leitlinie?

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Bestrahlung nach Prostatektomie: mehr Schaden als Nutzen?

02.05.2024 Prostatakarzinom Nachrichten

Eine adjuvante Radiotherapie nach radikaler Prostata-Op. bringt den Betroffenen wahrscheinlich keinen Vorteil. Im Gegenteil: Durch die Bestrahlung steigt offenbar das Risiko für Harn- und Stuhlinkontinenz.

Update Onkologie

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