Accumulation of CD103+ CD8+ T cells in a cutaneous melanoma micrometastasis

Katharina Hochheiser, Han Xian Aw Yeang, Teagan Wagner, Candani Tutuka, Andreas Behren, Jason Waithman, Christopher Angel, Paul J. Neeson, Thomas Gebhardt, David E. Gyorki

Research output: Contribution to journalArticle

Abstract

Objective: The immune system can halt cancer progression by suppressing outgrowth of clinically occult micrometastases in a state of cancer-immune equilibrium. Cutaneous melanoma provides a unique opportunity to study the immune contexture of such lesions, as miniscule skin metastases are accessible to clinical inspection and diagnostic biopsy. Methods: Here, we analysed by multiplex immunofluorescence microscopy samples from a melanoma patient presenting with an overt and an occult in-transit metastasis (ITM), the latter of which appeared as a small erythematous papule. Results: Microarchitecture and immune composition in the two lesions were vastly different. CD4+ and CD8+ T cells accumulated around the margin of the overt SOX10+ Melan A+ ITM but were largely excluded from the tumor centre. By contrast, the occult micrometastasis contained only few SOX10+ Melan A melanoma cells which were scattered within a dense infiltrate of T cells, including a prominent population of CD103+ CD8+ T cells resembling tissue-resident memory T (TRM) cells. Notably, almost every single melanoma cell in the micrometastasis was in close proximity to these TRM-like cells. Conclusion: Such results support the emerging concept that CD103+ CD8+ TRM cells are key mediators of cancer surveillance and imply an important function of these cells in controlling clinically occult micrometastases in humans.

Original languageEnglish
Article numbere1100
JournalClinical and Translational Immunology
Volume8
Issue number12
DOIs
Publication statusPublished - 25 Dec 2019

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Neoplasm Micrometastasis
Melanoma
T-Lymphocytes
Skin
MART-1 Antigen
Neoplasm Metastasis
Neoplasms
Fluorescence Microscopy
Immune System
Biopsy
Population

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Hochheiser, K., Aw Yeang, H. X., Wagner, T., Tutuka, C., Behren, A., Waithman, J., ... Gyorki, D. E. (2019). Accumulation of CD103+ CD8+ T cells in a cutaneous melanoma micrometastasis. Clinical and Translational Immunology, 8(12), [e1100]. https://doi.org/10.1002/cti2.1100
Hochheiser, Katharina ; Aw Yeang, Han Xian ; Wagner, Teagan ; Tutuka, Candani ; Behren, Andreas ; Waithman, Jason ; Angel, Christopher ; Neeson, Paul J. ; Gebhardt, Thomas ; Gyorki, David E. / Accumulation of CD103+ CD8+ T cells in a cutaneous melanoma micrometastasis. In: Clinical and Translational Immunology. 2019 ; Vol. 8, No. 12.
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abstract = "Objective: The immune system can halt cancer progression by suppressing outgrowth of clinically occult micrometastases in a state of cancer-immune equilibrium. Cutaneous melanoma provides a unique opportunity to study the immune contexture of such lesions, as miniscule skin metastases are accessible to clinical inspection and diagnostic biopsy. Methods: Here, we analysed by multiplex immunofluorescence microscopy samples from a melanoma patient presenting with an overt and an occult in-transit metastasis (ITM), the latter of which appeared as a small erythematous papule. Results: Microarchitecture and immune composition in the two lesions were vastly different. CD4+ and CD8+ T cells accumulated around the margin of the overt SOX10+ Melan A+ ITM but were largely excluded from the tumor centre. By contrast, the occult micrometastasis contained only few SOX10+ Melan A− melanoma cells which were scattered within a dense infiltrate of T cells, including a prominent population of CD103+ CD8+ T cells resembling tissue-resident memory T (TRM) cells. Notably, almost every single melanoma cell in the micrometastasis was in close proximity to these TRM-like cells. Conclusion: Such results support the emerging concept that CD103+ CD8+ TRM cells are key mediators of cancer surveillance and imply an important function of these cells in controlling clinically occult micrometastases in humans.",
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Hochheiser, K, Aw Yeang, HX, Wagner, T, Tutuka, C, Behren, A, Waithman, J, Angel, C, Neeson, PJ, Gebhardt, T & Gyorki, DE 2019, 'Accumulation of CD103+ CD8+ T cells in a cutaneous melanoma micrometastasis' Clinical and Translational Immunology, vol. 8, no. 12, e1100. https://doi.org/10.1002/cti2.1100

Accumulation of CD103+ CD8+ T cells in a cutaneous melanoma micrometastasis. / Hochheiser, Katharina; Aw Yeang, Han Xian; Wagner, Teagan; Tutuka, Candani; Behren, Andreas; Waithman, Jason; Angel, Christopher; Neeson, Paul J.; Gebhardt, Thomas; Gyorki, David E.

In: Clinical and Translational Immunology, Vol. 8, No. 12, e1100, 25.12.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Accumulation of CD103+ CD8+ T cells in a cutaneous melanoma micrometastasis

AU - Hochheiser, Katharina

AU - Aw Yeang, Han Xian

AU - Wagner, Teagan

AU - Tutuka, Candani

AU - Behren, Andreas

AU - Waithman, Jason

AU - Angel, Christopher

AU - Neeson, Paul J.

AU - Gebhardt, Thomas

AU - Gyorki, David E.

PY - 2019/12/25

Y1 - 2019/12/25

N2 - Objective: The immune system can halt cancer progression by suppressing outgrowth of clinically occult micrometastases in a state of cancer-immune equilibrium. Cutaneous melanoma provides a unique opportunity to study the immune contexture of such lesions, as miniscule skin metastases are accessible to clinical inspection and diagnostic biopsy. Methods: Here, we analysed by multiplex immunofluorescence microscopy samples from a melanoma patient presenting with an overt and an occult in-transit metastasis (ITM), the latter of which appeared as a small erythematous papule. Results: Microarchitecture and immune composition in the two lesions were vastly different. CD4+ and CD8+ T cells accumulated around the margin of the overt SOX10+ Melan A+ ITM but were largely excluded from the tumor centre. By contrast, the occult micrometastasis contained only few SOX10+ Melan A− melanoma cells which were scattered within a dense infiltrate of T cells, including a prominent population of CD103+ CD8+ T cells resembling tissue-resident memory T (TRM) cells. Notably, almost every single melanoma cell in the micrometastasis was in close proximity to these TRM-like cells. Conclusion: Such results support the emerging concept that CD103+ CD8+ TRM cells are key mediators of cancer surveillance and imply an important function of these cells in controlling clinically occult micrometastases in humans.

AB - Objective: The immune system can halt cancer progression by suppressing outgrowth of clinically occult micrometastases in a state of cancer-immune equilibrium. Cutaneous melanoma provides a unique opportunity to study the immune contexture of such lesions, as miniscule skin metastases are accessible to clinical inspection and diagnostic biopsy. Methods: Here, we analysed by multiplex immunofluorescence microscopy samples from a melanoma patient presenting with an overt and an occult in-transit metastasis (ITM), the latter of which appeared as a small erythematous papule. Results: Microarchitecture and immune composition in the two lesions were vastly different. CD4+ and CD8+ T cells accumulated around the margin of the overt SOX10+ Melan A+ ITM but were largely excluded from the tumor centre. By contrast, the occult micrometastasis contained only few SOX10+ Melan A− melanoma cells which were scattered within a dense infiltrate of T cells, including a prominent population of CD103+ CD8+ T cells resembling tissue-resident memory T (TRM) cells. Notably, almost every single melanoma cell in the micrometastasis was in close proximity to these TRM-like cells. Conclusion: Such results support the emerging concept that CD103+ CD8+ TRM cells are key mediators of cancer surveillance and imply an important function of these cells in controlling clinically occult micrometastases in humans.

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