Immunologic heterogeneity of tumor-infiltrating lymphocyte composition in primary melanoma

Sarah A. Weiss, Sung Won Han, Kevin Lui, Jeremy Tchack, Richard Shapiro, Russell Berman, Judy Zhong, Michelle Krogsgaard, Iman Osman, Farbod Darvishian

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Tumor-infiltrating lymphocytes (TILs) in primary melanomas are thought to represent the host antitumor immune response, but controversy exists over whether TILs offer independent prognostication of survival. We studied a cohort of 1241 patients with primary melanoma to assess the association of absent, nonbrisk, and brisk TIL grade with survival outcomes. We tested whether quantitative TIL counts using immunohistochemical lymphocyte markers CD3, CD45, and FOXP3 add prognostic value to TIL grading compared with histology alone in 15% of the cohort. To assess for intergroup immunologic heterogeneity among TIL grades, we investigated differential expression of 594 immunoregulatory genes in 67 primary melanomas. On histologic evaluation of 1241 primary melanomas, TILs were graded as absent (n = 388, 31%), nonbrisk (n = 330, 27%), and brisk (n = 523, 42%). Patients with brisk TILs had improved recurrence-free survival (P = .025) and overall survival (P = .006) compared with patients with nonbrisk and absent TILs, for which there were no differences in recurrence-free survival (P = .40) or overall survival (P = .41). TIL quantitation by immunohistochemistry did not improve prognostication compared with TIL grading on hematoxylin and eosin–stained sections. Melanomas with nonbrisk and absent TILs share similar immunoregulatory gene expression profiles. In contrast, melanomas with brisk TILs demonstrate upregulation of T-cell activation pathways and inhibition of upstream immune checkpoint regulators. The presence of TILs in primary melanomas represents a heterogeneous group, and caution in prognostic interpretation is warranted. Melanomas with brisk TILs are defined by an immunostimulatory gene expression profile and improved prognosis compared with melanomas with nonbrisk or absent TILs.

Original languageEnglish
Pages (from-to)116-125
Number of pages10
JournalHuman Pathology
Volume57
DOIs
Publication statusPublished - 2016 Nov 1

Fingerprint

Tumor-Infiltrating Lymphocytes
Melanoma
Survival
Transcriptome
Recurrence
Lymphocyte Count

Keywords

  • Brisk
  • Host immune response
  • Melanoma
  • Prognosis
  • Tumor-infiltrating lymphocytes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Immunologic heterogeneity of tumor-infiltrating lymphocyte composition in primary melanoma. / Weiss, Sarah A.; Han, Sung Won; Lui, Kevin; Tchack, Jeremy; Shapiro, Richard; Berman, Russell; Zhong, Judy; Krogsgaard, Michelle; Osman, Iman; Darvishian, Farbod.

In: Human Pathology, Vol. 57, 01.11.2016, p. 116-125.

Research output: Contribution to journalArticle

Weiss, SA, Han, SW, Lui, K, Tchack, J, Shapiro, R, Berman, R, Zhong, J, Krogsgaard, M, Osman, I & Darvishian, F 2016, 'Immunologic heterogeneity of tumor-infiltrating lymphocyte composition in primary melanoma', Human Pathology, vol. 57, pp. 116-125. https://doi.org/10.1016/j.humpath.2016.07.008
Weiss, Sarah A. ; Han, Sung Won ; Lui, Kevin ; Tchack, Jeremy ; Shapiro, Richard ; Berman, Russell ; Zhong, Judy ; Krogsgaard, Michelle ; Osman, Iman ; Darvishian, Farbod. / Immunologic heterogeneity of tumor-infiltrating lymphocyte composition in primary melanoma. In: Human Pathology. 2016 ; Vol. 57. pp. 116-125.
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AU - Weiss, Sarah A.

AU - Han, Sung Won

AU - Lui, Kevin

AU - Tchack, Jeremy

AU - Shapiro, Richard

AU - Berman, Russell

AU - Zhong, Judy

AU - Krogsgaard, Michelle

AU - Osman, Iman

AU - Darvishian, Farbod

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AB - Tumor-infiltrating lymphocytes (TILs) in primary melanomas are thought to represent the host antitumor immune response, but controversy exists over whether TILs offer independent prognostication of survival. We studied a cohort of 1241 patients with primary melanoma to assess the association of absent, nonbrisk, and brisk TIL grade with survival outcomes. We tested whether quantitative TIL counts using immunohistochemical lymphocyte markers CD3, CD45, and FOXP3 add prognostic value to TIL grading compared with histology alone in 15% of the cohort. To assess for intergroup immunologic heterogeneity among TIL grades, we investigated differential expression of 594 immunoregulatory genes in 67 primary melanomas. On histologic evaluation of 1241 primary melanomas, TILs were graded as absent (n = 388, 31%), nonbrisk (n = 330, 27%), and brisk (n = 523, 42%). Patients with brisk TILs had improved recurrence-free survival (P = .025) and overall survival (P = .006) compared with patients with nonbrisk and absent TILs, for which there were no differences in recurrence-free survival (P = .40) or overall survival (P = .41). TIL quantitation by immunohistochemistry did not improve prognostication compared with TIL grading on hematoxylin and eosin–stained sections. Melanomas with nonbrisk and absent TILs share similar immunoregulatory gene expression profiles. In contrast, melanomas with brisk TILs demonstrate upregulation of T-cell activation pathways and inhibition of upstream immune checkpoint regulators. The presence of TILs in primary melanomas represents a heterogeneous group, and caution in prognostic interpretation is warranted. Melanomas with brisk TILs are defined by an immunostimulatory gene expression profile and improved prognosis compared with melanomas with nonbrisk or absent TILs.

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