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. 2021 Jul:151:25-34.
doi: 10.1016/j.ejca.2021.03.053. Epub 2021 May 4.

Intratumour microbiome associated with the infiltration of cytotoxic CD8+ T cells and patient survival in cutaneous melanoma

Gongjian Zhu  1 , Haixiang Su  2 , Caroline H Johnson  3 , Sajid A Khan  4 , Harriet Kluger  5 , Lingeng Lu  6
Affiliations

Intratumour microbiome associated with the infiltration of cytotoxic CD8+ T cells and patient survival in cutaneous melanoma

Gongjian Zhu et al. Eur J Cancer. 2021 Jul.

Abstract

Objective: The gut microbiome plays an important role in systemic inflammation and immune response. Microbes can translocate and reside in tumour niches. However, it is unclear how the intratumour microbiome affects immunity in human cancer. The purpose of this study was to investigate the association between intratumour bacteria, infiltrating CD8+ T cells and patient survival in cutaneous melanoma.

Methods: Using The Cancer Genome Altas's cutaneous melanoma RNA sequencing data, levels of intratumour bacteria and infiltrating CD8+ T cells were determined. Correlation between intratumour bacteria and infiltrating CD8+ T cells or chemokine gene expression and survival analysis of infiltrating CD8+ T cells and Lachnoclostridium in cutaneous melanoma were performed.

Results: Patients with low levels of CD8+ T cells have significantly shorter survival than those with high levels. The adjusted hazard ratio was 1.57 (low vs high) (95% confidence interval: 1.17-2.10, p = 0.002). Intratumour bacteria of the Lachnoclostridium genus ranked top in a positive association with infiltrating CD8+ T cells (correlation coefficient = 0.38, p = 9.4 × 10-14), followed by Gelidibacter (0.31, p = 1.13 × 10-9), Flammeovirga (0.29, p = 1.96 × 10-8) and Acinetobacter (0.28, p = 8.94 × 10-8). These intratumour genera positively correlated with chemokine CXCL9, CXCL10 and CCL5 expression. The high Lachnoclostridium load significantly reduced the mortality risk (p = 0.0003). However, no statistically significant correlation was observed between intratumour Lachnoclostridium abundance and the levels of either NK, B or CD4+ T cells.

Conclusion: Intratumour-residing gut microbiota could modulate chemokine levels and affect CD8+ T-cell infiltration, consequently influencing patient survival in cutaneous melanoma. Manipulating the intratumour gut microbiome may benefit patient outcomes for those undergoing immunotherapy.

Keywords: CD8+ T cells; Gut microbiome; Intratumour bacteria; Melanoma; Prognosis.

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Conflict of interest statement

Conflict of interest statement H.K. has received research funding (institutional funding) from Merck, Bristol Myers Squibb and Apexigen and personal fees from Corvus, Nektar, Pfizer, Iovance, Immunocore, Celldex, Array BioPharma, Merck, Bristol Myers Squibb, Instil Bio, ElevateBio, Clinigen and Shionogi. The other authors have no conflict of interest to declare.

Figures

Figure 1.
Figure 1.
Association between intra-tumor bacteria and infiltrated CD8+ T cells in cutaneous melanoma. Bar plot showing the correlation coefficients for top 18 intra-tumor bacteria genera with a p value < 0.001.
Figure 2.
Figure 2.
Kaplan-Meier overall survival curves stratified by intra-tumor Lachnoclostridium abundance in cutaneous melanoma. Patients with high Lachnoclostridium showed superior overall survival than those with low one (log-rank p value = 0.009).
See this image and copyright information in PMC

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