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Lymphocyte recruitment into the tumor site is altered in patients with MSI-H colon cancer

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Abstract

The ability of the host to mount an appropriate immune response to aberrant cells is one factor that determines prognosis in cancer patients. Naturally occurring regulatory T cells (T regs; CD4+ CD25+ cells) are key regulators of peripheral tolerance. It has been suggested that high levels of T regs are detrimental to the patient in some forms of cancer, but the role of these antigen-specific cells in individuals with colorectal cancers with high levels of microsatellite instability is unknown. Herein, we examined the ability of individuals with MSI-H or microsatellite stable colon cancer to recruit lymphocytes to the tumor site. Immunohistochemical staining was performed on archived paraffin-embedded specimens from a total of 38 individuals with MSI-H (n = 25) or MSS (n = 13) colon cancers to determine the proportion of CD3+, CD8+ and CD25+ cells infiltrating the tumor site. Patients with MSI-H colon cancers had increased percentages of CD8+ TILs (cytotoxic T cells) as compared to individuals with MSS colon cancer (47.3 vs. 24.04% of the infiltrate CD8+, respectively). No differences in the levels of CD25+ T cells were observed between individuals with MSI-H colon cancers and MSS colon cancers (0.53 vs. 0.54% CD25+, respectively). Together, these data suggest that the survival advantage enjoyed by patients with MSI-H colorectal cancer may, in part, be attributed to the increased cytolytic response, but not to an antigen-specific immunosuppressive response in MSS patients.

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Abbreviations

CRC:

Colorectal cancer

HNPCC:

Hereditary nonpolyposis colorectal cancer

HPF:

High power field

MSI-H:

High level of microsatellite instability

MSS:

Microsatellite stable

T regs:

Regulatory T cells

TILs:

Tumor infiltrating lymphocytes

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Acknowledgments

Grant support This research was supported by revenue from Nebraska Cigarette Taxes awarded to Creighton University by the Nebraska, Department of Health and Human Services (LB 595; KMD, HTL). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the State of Nebraska or the Nebraska Department of Health and Human Services. The National Institutes of Health Early Detection Research Network Grant #1U01CA86389 also provided support for these studies. Dr. Henry Lynch holds the Charles F. and Mary C. Heider Chair in Cancer Research at Creighton University. This investigation was conducted in a facility constructed with support from Research Facilities Improvement Program (1 C06 RR17417-01) from the National Center for Research Resources, National Institutes of Health.

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Authors and Affiliations

  1. Department of Medical Microbiology and Immunology, Creighton University School of Medicine, 2500 California Plaza, Omaha, NE, 68178, USA

    Kristen M. Drescher

  2. Department of Pathology, Creighton University School of Medicine, Omaha, NE, USA

    Poonam Sharma & Zoran Gatalica

  3. Osteoporosis Research Center, Creighton University School of Medicine, Omaha, NE, USA

    Patrice Watson

  4. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    Stephen N. Thibodeau

  5. Department of Preventative Medicine, Creighton University School of Medicine, Omaha, NE, USA

    Henry T. Lynch

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  1. Kristen M. Drescher
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  2. Poonam Sharma
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  3. Patrice Watson
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  4. Zoran Gatalica
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  5. Stephen N. Thibodeau
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  6. Henry T. Lynch
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Correspondence to Kristen M. Drescher.

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Kristen M. Drescher and Poonam Sharma have been contributed equally to this study.

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Drescher, K.M., Sharma, P., Watson, P. et al. Lymphocyte recruitment into the tumor site is altered in patients with MSI-H colon cancer. Familial Cancer 8, 231–239 (2009). https://doi.org/10.1007/s10689-009-9233-0

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