Tumor Mutation Burden and Structural Chromosomal Aberrations Are Not Associated with T-cell Density or Patient Survival in Acral, Mucosal, and Cutaneous Melanomas

Tumor Mutation Burden and Structural Chromosomal Aberrations Are Not Associated with T-cell Density or Patient Survival in Acral, Mucosal, and Cutaneous Melanomas.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1158/2326-6066.CIR-19-0835
Journal or Publication Title: Cancer Immunology Research
Volume: 8
Number: 11
Page Range: pp. 1346-1353
Date: 2020
Divisions: Human Viral and Cancer Immunology
Depositing User: General Admin
Identification Number: 10.1158/2326-6066.CIR-19-0835
ISSN: 2326-6066
Date Deposited: 04 Jan 2021 01:19
Abstract:

Tumor mutation burden (TMB) has been proposed as a key determinant of immunogenicity in several cancers, including melanoma. The evidence presented thus far, however, is often contradictory and based mostly on RNA-sequencing data for the quantification of immune cell phenotypes. Few studies have investigated TMB across acral, mucosal, and cutaneous melanoma subtypes, which are known to have different TMB. It is also unknown whether chromosomal structural mutations [structural variant (SV) mutations] contribute to the immunogenicity in acral and mucosal melanomas where such aberrations are common. We stained 151 cutaneous and 35 acral and mucosal melanoma patient samples using quantitative IHC and correlated immune infiltrate phenotypes with TMB and other genomic profiles. TMB and SVs did not correlate with the densities of CD8+ lymphocytes, CD103+ tumor-resident T cells (Trm), CD45RO+ cells, and other innate and adaptive immune cell subsets in cutaneous and acral/mucosal melanoma tumors, respectively, including in analyses restricted to the site of disease and in a validation cohort. In 43 patients with stage III treatment-naïve cutaneous melanoma, we found that the density of immune cells, particularly Trm, was significantly associated with patient survival, but not with TMB. Overall, TMB and chromosomal structural aberrations are not associated with protective antitumor immunity in treatment-naïve melanoma.

Creators:
Creators
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Edwards, Jarem
UNSPECIFIED
Ferguson, Peter M.
UNSPECIFIED
Lo, Serigne N.
UNSPECIFIED
Pires da Silva, Inês
UNSPECIFIED
Colebatch, Andrew J.
UNSPECIFIED
Lee, Hansol
UNSPECIFIED
Saw, Robyn P.M.
UNSPECIFIED
Thompson, John F.
UNSPECIFIED
Menzies, Alexander M.
UNSPECIFIED
Long, Georgina V.
UNSPECIFIED
Newell, Felicity
UNSPECIFIED
Pearson, John V.
UNSPECIFIED
Waddell, Nicola
UNSPECIFIED
Hayward, Nicholas K.
UNSPECIFIED
Johansson, Peter A.
UNSPECIFIED
Mann, Graham J.
UNSPECIFIED
Scolyer, Richard A.
UNSPECIFIED
Palendira, Umaimainthan
UNSPECIFIED
Wilmott, James S.
UNSPECIFIED
Last Modified: 04 Jan 2021 01:19
URI: https://eprints.centenary.org.au/id/eprint/788

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