Top

Clinical and Translational Oncology

Published in:

01-03-2014 | Research Article

The clinical significance of memory T cells and its subsets in gastric cancer

Authors: R. Zhang, F. Li, H. Li, J. Yu, X. Ren

Published in: Clinical and Translational Oncology | Issue 3/2014

Abstract

Background

Long life of memory T cell (Tm) determines its crucial role in the carcinogenesis and carcinogenic progression which usually take long time. The Tm compartment contains two populations, central memory T cells (Tcm) and effector memory T cells (Tem), based on their phenotypic markers, functional attributes, and migratory properties.

Methods

We investigated the subsets of the Tm in peripheral blood and tumor microenvironments in patients with gastric cancer by flow cytometry, and aimed to explore the correlation between the Tm and clinicopathologic features of gastric cancer.

Results

The percentages of CD4⁺/CD8⁺ Tm and CD4⁺/CD8⁺ Tcm in peripheral blood from gastric cancer patients were statistically lower, whereas the percentages of CD4⁺/CD8⁺ Tem were significantly higher than healthy controls. The proportion of CD4⁺/CD8⁺ Tcm increased after tumor resection, while the percentage of the CD4⁺/CD8⁺ Tem decreased significantly. Significant associations were detected between the peripheral CD4⁺/CD8⁺ Tm and clinical stage, as well as the CD8⁺ Tcm and clinical stage and nodal involvement. Tumor infiltrating CD8⁺ Tm expressed both central and effector memory phenotypes, whereas CD4⁺ Tm displayed predominantly an effector memory phenotype. Higher percentages of tumor infiltrating CD4⁺/CD8⁺ Tm were significantly associated with the early disease stage.

Conclusions

Tm and its subsets were good immune indicators for the disease stage of gastric cancer. The proportion of Tm subsets may reflect the immune suppressive and immune response to the tumor associated antigen.

Sallusto F, Lenig D, Forster R, Lipp M, Lanzavecchia A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature. 1999;401(6754):708–12.PubMedCrossRef

Manjunath N, Shankar P, Wan J, Weninger W, Crowley MA, Hieshima K, et al. Effector differentiation is not prerequisite for generation of memory cytotoxic T lymphocytes. J Clin Invest. 2001;108(6):871–8.PubMedCentralPubMedCrossRef

Wherry EJ, Teichgraber V, Becker TC, Masopust D, Kaech SM, Antia R, et al. Lineage relationship and protective immunity of memory CD8 T cell subsets. Nat Immunol. 2003;4(3):225–34.PubMedCrossRef

Klebanoff CA, Gattinoni L, Torabi-Parizi P, Kerstann K, Cardones AR, Finkelstein SE, et al. Central memory self/tumor-reactive CD8⁺ T cells confer superior antitumor immunity compared with effector memory T cells. Proc Natl Acad Sci USA. 2005;102(27):9571–6.PubMedCrossRef

Klebanoff CA, Gattinoni L, Restifo NP. CD8⁺ T-cell memory in tumor immunology and immunotherapy. Immunol Rev. 2006;211:214–24.PubMedCentralPubMedCrossRef

Lalvani A, Brookes R, Hambleton S, Britton WJ, Hill AV, McMichael AJ. Rapid effector function in CD8⁺ memory T cells. J Exp Med. 1997;186(6):859–65.PubMedCentralPubMedCrossRef

Novy P, Quigley M, Huang X, Yang Y. CD4 T cells are required for CD8 T cell survival during both primary and memory recall responses. J Immunol. 2007;179(12):8243–51.PubMed

Hwang ML, Lukens JR, Bullock TN. Cognate memory CD4+ T cells generated with dendritic cell priming influence the expansion, trafficking, and differentiation of secondary CD8+ T cells and enhance tumor control. J Immunol. 2007;179(9):5829–38.PubMed

Merkenschlager M, Terry L, Edwards R, Beverley PC. Limiting dilution analysis of proliferative responses in human lymphocyte populations defined by the monoclonal antibody UCHL1: implications for differential CD45 expression in T cell memory formation. Eur J Immunol. 1988;18(11):1653–61.PubMedCrossRef

10.

Hotta K, Sho M, Fujimoto K, Shimada K, Yamato I, Anai S, et al. Prognostic significance of CD45RO+ memory T cells in renal cell carcinoma. Br J Cancer. 2011;105(8):1191–6.PubMedCentralPubMedCrossRef

11.

Xiang R, Lode HN, Gillies SD, Reisfeld RA. T cell memory against colon carcinoma is long-lived in the absence of antigen. J Immunol. 1999;163(7):3676–83.PubMed

12.

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.PubMedCrossRef

13.

Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.PubMedCrossRef

14.

Belov L, Zhou J, Christopherson RI. Cell surface markers in colorectal cancer prognosis. Int J Mol Sci. 2010;12(1):78–113.PubMedCentralPubMedCrossRef

15.

Pages F, Galon J, Dieu-Nosjean MC, Tartour E, Sautes-Fridman C, Fridman WH. Immune infiltration in human tumors: a prognostic factor that should not be ignored. Oncogene. 2010;29(8):1093–102.PubMedCrossRef

16.

Mlecnik B, Tosolini M, Charoentong P, Kirilovsky A, Bindea G, Berger A, et al. Biomolecular network reconstruction identifies T-cell homing factors associated with survival in colorectal cancer. Gastroenterology. 2010;138(4):1429–40.PubMedCrossRef

17.

Bindea G, Mlecnik B, Fridman WH, Galon J. The prognostic impact of anti-cancer immune response: a novel classification of cancer patients. Semin Immunopathol. 2011;33(4):335–40.PubMedCentralPubMedCrossRef

18.

Hara M, Matsuzaki Y, Shimizu T, Tomita M, Ayabe T, Enomoto Y, et al. Preoperative peripheral naive/memory ratio and prognosis of nonsmall-cell lung cancer patients. Ann Thorac Cardiovasc Surg. 2007;13(6):384–90.PubMed

19.

Kuss I, Schaefer C, Godfrey TE, Ferris RL, Harris JM, Gooding W, et al. Recent thymic emigrants and subsets of naive and memory T cells in the circulation of patients with head and neck cancer. Clin Immunol. 2005;116(1):27–36.PubMedCrossRef

20.

Sallusto F, Lanzavecchia A. Exploring pathways for memory T cell generation. J Clin Invest. 2001;108(6):805–6.PubMedCentralPubMedCrossRef

21.

Barbieri C, Fujisawa MM, Yasuda CL, Metze IL, Oliveira EC, Santos LM, et al. Effect of surgical treatment on the cellular immune response of gastric cancer patients. Braz J Med Biol Res. 2003;36(3):339–45.PubMedCrossRef

22.

Tanel A, Fonseca SG, Yassine-Diab B, Bordi R, Zeidan J, Shi Y, et al. Cellular and molecular mechanisms of memory T-cell survival. Expert Rev Vaccin. 2009;8(3):299–312.CrossRef

23.

Kaech SM, Wherry EJ, Ahmed R. Effector and memory T-cell differentiation: implications for vaccine development. Nat Rev Immunol. 2002;2(4):251–62.PubMedCrossRef

24.

Rauser S, Langer R, Tschernitz S, Gais P, Jutting U, Feith M, 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.PubMedCentralPubMedCrossRef

25.

Pages F, Berger A, Camus M, Sanchez-Cabo F, Costes A, Molidor R, et al. Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med. 2005;353(25):2654–66.PubMedCrossRef

26.

Broussard EK, Disis ML. TNM staging in colorectal cancer: T is for T cell and M is for memory. J Clin Oncol. 2011;29(6):601–3.PubMedCrossRef

27.

Nosho K, Baba Y, Tanaka N, Shima K, Hayashi M, Meyerhardt JA, et al. Tumour-infiltrating T-cell subsets, molecular changes in colorectal cancer, and prognosis: cohort study and literature review. J Pathol. 2010;222(4):350–66.PubMedCentralPubMedCrossRef

28.

Lee HE, Chae SW, Lee YJ, Kim MA, Lee HS, Lee BL, et al. Prognostic implications of type and density of tumour-infiltrating lymphocytes in gastric cancer. Br J Cancer. 2008;99(10):1704–11.PubMedCentralPubMedCrossRef

Title: The clinical significance of memory T cells and its subsets in gastric cancer
Authors: R. Zhang
F. Li
H. Li
J. Yu
X. Ren
Publication date: 01-03-2014
Publisher: Springer Milan
Published in: Clinical and Translational Oncology / Issue 3/2014
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI: https://doi.org/10.1007/s12094-013-1066-5

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 3/2014

Cost analysis of skeletal-related events in Spanish patients with bone metastases from solid tumours

Guidelines for biomarker testing in gastroenteropancreatic neuroendocrine neoplasms: a national consensus of the Spanish Society of Pathology and the Spanish Society of Medical Oncology

Combined preoperative CEA and CD44v6 improves prognostic value in patients with stage I and stage II colorectal cancer

Changes in the immune cell population and cell proliferation in peripheral blood after gemcitabine-based chemotherapy for pancreatic cancer

Recommendations of a group of experts for the pathological assessment of tumour regression of liver metastases of colorectal cancer and damage of non-tumour liver tissue after neoadjuvant therapy

HIV-1 viral protein R downregulates Ebp1 and stabilizes p53 in glioblastoma U87MG cells

Keynote webinar | Spotlight on antibody–drug conjugates in cancer