Skip to main content
Erschienen in: Annals of Surgical Oncology 5/2012

01.05.2012 | Translational Research and Biomarkers

The Immunological Impact of Neoadjuvant Chemotherapy on the Tumor Microenvironment of Esophageal Squamous Cell Carcinoma

verfasst von: Takahiro Tsuchikawa, MD, Masaki Miyamoto MD, Yoshiyuki Yamamura, MD, Toshiaki Shichinohe, MD, Satoshi Hirano, MD, Satoshi Kondo, MD

Erschienen in: Annals of Surgical Oncology | Ausgabe 5/2012

Einloggen, um Zugang zu erhalten

Abstract

Background

Esophageal cancer is an aggressive cancer with poor prognosis. However, little is known about the immune response in the tumor microenvironment after neoadjuvant chemotherapy.

Purpose

To investigate the immunological impact of neoadjuvant chemotherapy in the tumor microenvironment of esophageal squamous cell carcinoma.

Methods

Eighteen patients with esophageal squamous cell carcinoma with and without neoadjuvant chemotherapy were analyzed using immunohistochemical methods for human leukocyte antigen (HLA) class I heavy chain, CD4-, CD8-, and Foxp3-positive cell infiltration.

Results

The number of CD4 T cells in the stroma and within the cancer nest was significantly higher in the neoadjuvant chemotherapy group. The number of CD8 T cells in the stroma was significantly higher in the neoadjuvant chemotherapy group. HLA class I expression was more downregulated in the control group compared with the neoadjuvant chemotherapy group.

Conclusion

Neoadjuvant chemotherapy utilizing 5-fluorouracil and cisplatin in esophageal squamous cell carcinoma is useful to induce CD4 and CD8 T lymphocytes in the tumor microenvironment and to maintain HLA class I expression levels in combination with its direct cytotoxic effects.
Literatur
1.
Zurück zum Zitat Ando N, Iizuka T, Ide H, et al. Surgery plus chemotherapy compared with surgery alone for localized squamous cell carcinoma of the thoracic esophagus: a Japan Clinical Oncology Group Study—JCOG9204. J Clin Oncol. 2003;21:4592–6.PubMedCrossRef Ando N, Iizuka T, Ide H, et al. Surgery plus chemotherapy compared with surgery alone for localized squamous cell carcinoma of the thoracic esophagus: a Japan Clinical Oncology Group Study—JCOG9204. J Clin Oncol. 2003;21:4592–6.PubMedCrossRef
2.
Zurück zum Zitat Campbell NP, Villaflor VM. Neoadjuvant treatment of esophageal cancer. World J Gastroenterol. 2010;16:3793–803.PubMedCrossRef Campbell NP, Villaflor VM. Neoadjuvant treatment of esophageal cancer. World J Gastroenterol. 2010;16:3793–803.PubMedCrossRef
3.
Zurück zum Zitat Higuchi K, Koizumi W, Tanabe S, et al. Current management of esophageal squamous-cell carcinoma in Japan and other countries. Gastrointest Cancer Res. 2009;3:153–61.PubMed Higuchi K, Koizumi W, Tanabe S, et al. Current management of esophageal squamous-cell carcinoma in Japan and other countries. Gastrointest Cancer Res. 2009;3:153–61.PubMed
4.
Zurück zum Zitat Cho Y, Miyamoto M, Kato K, et al. CD4+ and CD8+ T cells cooperate to improve prognosis of patients with esophageal squamous cell carcinoma. Cancer Res. 2003;63:1555–9.PubMed Cho Y, Miyamoto M, Kato K, et al. CD4+ and CD8+ T cells cooperate to improve prognosis of patients with esophageal squamous cell carcinoma. Cancer Res. 2003;63:1555–9.PubMed
5.
Zurück zum Zitat Yoshioka T, Miyamoto M, Cho Y, et al. Infiltrating regulatory T cell numbers is not a factor to predict patient’s survival in oesophageal squamous cell carcinoma. Br J Cancer. 2008;98:1258–63.PubMedCrossRef Yoshioka T, Miyamoto M, Cho Y, et al. Infiltrating regulatory T cell numbers is not a factor to predict patient’s survival in oesophageal squamous cell carcinoma. Br J Cancer. 2008;98:1258–63.PubMedCrossRef
6.
Zurück zum Zitat Canna K, Hilmy M, McMillan DC, Smith GW, McKee RF, McArdle CS, et al. The relationship between tumour proliferative activity, the systemic inflammatory response and survival in patients undergoing curative resection for colorectal cancer. Colorectal Dis. 2008;10:663–7.PubMedCrossRef Canna K, Hilmy M, McMillan DC, Smith GW, McKee RF, McArdle CS, et al. The relationship between tumour proliferative activity, the systemic inflammatory response and survival in patients undergoing curative resection for colorectal cancer. Colorectal Dis. 2008;10:663–7.PubMedCrossRef
7.
Zurück zum Zitat McMillan DC, Canna K, McArdle CS. Systemic inflammatory response predicts survival following curative resection of colorectal cancer. Br J Surg. 2003;90:215–9.PubMedCrossRef McMillan DC, Canna K, McArdle CS. Systemic inflammatory response predicts survival following curative resection of colorectal cancer. Br J Surg. 2003;90:215–9.PubMedCrossRef
8.
Zurück zum Zitat Sobin LH, Wittekind Ch. International Union Against Cancer. TNM classification of malignant tumors. New York: Wiley-Liss; 2002. P. 60–4. Sobin LH, Wittekind Ch. International Union Against Cancer. TNM classification of malignant tumors. New York: Wiley-Liss; 2002. P. 60–4.
9.
Zurück zum Zitat Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–16.PubMedCrossRef Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–16.PubMedCrossRef
10.
Zurück zum Zitat Evans DB, Rich TA, Byrd DR, et al. Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas. Arch Surg. 1992;127:1335–9.PubMedCrossRef Evans DB, Rich TA, Byrd DR, et al. Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas. Arch Surg. 1992;127:1335–9.PubMedCrossRef
11.
Zurück zum Zitat Wada S, Yoshimura K, Hipkiss EL, et al. Cyclophosphamide augments antitumor immunity: studies in an autochthonous prostate cancer model. Cancer Res. 2009;69:4309–18.PubMedCrossRef Wada S, Yoshimura K, Hipkiss EL, et al. Cyclophosphamide augments antitumor immunity: studies in an autochthonous prostate cancer model. Cancer Res. 2009;69:4309–18.PubMedCrossRef
12.
Zurück zum Zitat Garnett CT, Schlom J, Hodge JW. Combination of docetaxel and recombinant vaccine enhances T-cell responses and antitumor activity: effects of docetaxel on immune enhancement. Clin Cancer Res. 2008;14:3536–44.PubMedCrossRef Garnett CT, Schlom J, Hodge JW. Combination of docetaxel and recombinant vaccine enhances T-cell responses and antitumor activity: effects of docetaxel on immune enhancement. Clin Cancer Res. 2008;14:3536–44.PubMedCrossRef
13.
Zurück zum Zitat Rozková D, Tiserová H, Fucíková J, et al. FOCUS on FOCIS: combined chemo-immunotherapy for the treatment of hormone-refractory metastatic prostate cancer. Clin Immunol. 2009;131:1–10.PubMedCrossRef Rozková D, Tiserová H, Fucíková J, et al. FOCUS on FOCIS: combined chemo-immunotherapy for the treatment of hormone-refractory metastatic prostate cancer. Clin Immunol. 2009;131:1–10.PubMedCrossRef
14.
Zurück zum Zitat Lesterhuis WJ, de Vries IJ, Aarntzen EA, et al. A pilot study on the immunogenicity of dendritic cell vaccination during adjuvant oxaliplatin/capecitabine chemotherapy in colon cancer patients. Br J Cancer. 2010;103:1415–21.PubMedCrossRef Lesterhuis WJ, de Vries IJ, Aarntzen EA, et al. A pilot study on the immunogenicity of dendritic cell vaccination during adjuvant oxaliplatin/capecitabine chemotherapy in colon cancer patients. Br J Cancer. 2010;103:1415–21.PubMedCrossRef
15.
Zurück zum Zitat Obeid M, Tesniere A, Ghiringhelli F, et al. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med. 2007;13:54–61.PubMedCrossRef Obeid M, Tesniere A, Ghiringhelli F, et al. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med. 2007;13:54–61.PubMedCrossRef
16.
Zurück zum Zitat Obeid M, Tesniere A, Panaretakis T, et al. Ecto-calreticulin in immunogenic chemotherapy. Immunol Rev. 2007;220:22–34.PubMedCrossRef Obeid M, Tesniere A, Panaretakis T, et al. Ecto-calreticulin in immunogenic chemotherapy. Immunol Rev. 2007;220:22–34.PubMedCrossRef
17.
Zurück zum Zitat Chaput N, De Botton S, Obeid M, et al. Molecular determinants of immunogenic cell death: surface exposure of calreticulin makes the difference. J Mol Med. 2007;85:1069–76.PubMedCrossRef Chaput N, De Botton S, Obeid M, et al. Molecular determinants of immunogenic cell death: surface exposure of calreticulin makes the difference. J Mol Med. 2007;85:1069–76.PubMedCrossRef
18.
Zurück zum Zitat Sims GP, Rowe DC, Rietdijk ST, Herbst R, Coyle AJ. HMGB1 and RAGE in inflammation and cancer. Annu Rev Immunol. 2010;28:367–88.PubMedCrossRef Sims GP, Rowe DC, Rietdijk ST, Herbst R, Coyle AJ. HMGB1 and RAGE in inflammation and cancer. Annu Rev Immunol. 2010;28:367–88.PubMedCrossRef
19.
Zurück zum Zitat Brode S, Cooke A. Immune-potentiating effects of the chemotherapeutic drug cyclophosphamide. Crit Rev Immunol. 2008;28:109–26.PubMed Brode S, Cooke A. Immune-potentiating effects of the chemotherapeutic drug cyclophosphamide. Crit Rev Immunol. 2008;28:109–26.PubMed
20.
Zurück zum Zitat Schnurr M, Chen Q, Shin A, et al. Tumor antigen processing and presentation depend critically on dendritic cell type and the mode of antigen delivery. Blood. 2005;105:2465–72.PubMedCrossRef Schnurr M, Chen Q, Shin A, et al. Tumor antigen processing and presentation depend critically on dendritic cell type and the mode of antigen delivery. Blood. 2005;105:2465–72.PubMedCrossRef
21.
Zurück zum Zitat Ladányi A, Kiss J, Somlai B, et al. Density of DC-LAMP(+) mature dendritic cells in combination with activated T lymphocytes infiltrating primary cutaneous melanoma is a strong independent prognostic factor. Cancer Immunol Immunother. 2007;56:1459–69.PubMedCrossRef Ladányi A, Kiss J, Somlai B, et al. Density of DC-LAMP(+) mature dendritic cells in combination with activated T lymphocytes infiltrating primary cutaneous melanoma is a strong independent prognostic factor. Cancer Immunol Immunother. 2007;56:1459–69.PubMedCrossRef
22.
Zurück zum Zitat Bembenek A, Li J, Loddenkemper C, Kemmner W, Stein H, Wernecke KD, et al. Presence of mature DC-Lamp+ dendritic cells in sentinel and non-sentinel lymph nodes of breast cancer patients. Eur J Surg Oncol. 2008;34:514–8.PubMedCrossRef Bembenek A, Li J, Loddenkemper C, Kemmner W, Stein H, Wernecke KD, et al. Presence of mature DC-Lamp+ dendritic cells in sentinel and non-sentinel lymph nodes of breast cancer patients. Eur J Surg Oncol. 2008;34:514–8.PubMedCrossRef
23.
Zurück zum Zitat Rauser S, Langer R, Tschernitz S, et al. High number of CD45RO+ tumor infiltrating lymphocytes is an independent prognostic factor in non-metastasized (stage I-IIA) esophageal adenocarcinoma. BMC Cancer. 2010;10:608–16.PubMedCrossRef Rauser S, Langer R, Tschernitz S, et al. High number of CD45RO+ tumor infiltrating lymphocytes is an independent prognostic factor in non-metastasized (stage I-IIA) esophageal adenocarcinoma. BMC Cancer. 2010;10:608–16.PubMedCrossRef
Metadaten
Titel
The Immunological Impact of Neoadjuvant Chemotherapy on the Tumor Microenvironment of Esophageal Squamous Cell Carcinoma
verfasst von
Takahiro Tsuchikawa, MD
Masaki Miyamoto MD
Yoshiyuki Yamamura, MD
Toshiaki Shichinohe, MD
Satoshi Hirano, MD
Satoshi Kondo, MD
Publikationsdatum
01.05.2012
Verlag
Springer-Verlag
Erschienen in
Annals of Surgical Oncology / Ausgabe 5/2012
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-011-1906-x

Weitere Artikel der Ausgabe 5/2012

Annals of Surgical Oncology 5/2012 Zur Ausgabe

Update Chirurgie

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

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

CME: 2 Punkte

Prof. Dr. med. Gregor Antoniadis Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis
Berufsverband der Deutschen Chirurgie e.V.

S2e-Leitlinie „Distale Radiusfraktur“

CME: 2 Punkte

Dr. med. Benjamin Meyknecht, PD Dr. med. Oliver Pieske Das Webinar S2e-Leitlinie „Distale Radiusfraktur“ beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske
Dr. med. Benjamin Meyknecht
Berufsverband der Deutschen Chirurgie e.V.

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

CME: 2 Punkte

Dr. med. Mihailo Andric
Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric
Berufsverband der Deutschen Chirurgie e.V.