Association of tumor-infiltrating T-cell density with molecular subtype, racial ancestry and clinical outcomes in prostate cancer

Abstract

The inflammatory microenvironment plays an important role in the pathogenesis and progression of tumors and may be associated with somatic genomic alterations. We examined the association of tumor infiltrating T-cell density with clinical-pathologic variables, tumor molecular subtype and oncologic outcomes in surgically-treated primary prostate cancer occurring in patients of European-American or African-American ancestry. We evaluated 312 primary prostate tumors, enriched for patients with African-American ancestry and high grade disease. Tissue microarrays were immunostained for CD3, CD8 and FOXP3 and were previously immunostained for ERG and PTEN using genetically validated protocols. Image analysis for quantification of T-cell density in tissue microarray tumor spots was performed. Automated quantification of T-cell densities in tumor-containing regions of tissue microarray spots and standard histologic sections were correlated (r=0.73, p<0.00001) and there was good agreement between visual and automated T-cell density counts on tissue microarray spots (r=0.93, p<0.00001). There was a significant correlation between CD3+, CD8+ and FOXP3+ T-cell densities (p<0.00001), but these were not associated with most clinical or pathologic variables. Increased T-cell density was significantly associated with ERG positivity (median 309 vs 188 CD3+ T-cells/mm2; p=0.0004) and also with PTEN loss (median 317 vs 192 CD3+ T-cells/mm2; p=0.001) in the combined cohort of matched European-American and African-American ancestry patients. The same association or a similar trend was present in patients of both ancestries when analyzed separately. When the African-American patients from the matched race set were combined with a separate high grade set of African-American cases, there was a weak association of increased FOXP3+ T-cell densities with increased risk of metastasis in multivariable analysis. Though high T-cell density is associated with specific molecular subclasses of prostate cancer, we did not find an association of T-cell density with racial ancestry.

The establishment of immune infiltration based novel recurrence predicting nomogram in prostate cancer

“…[15][16][17][18][19] Clinical outcomes and the potential mechanisms involving PCa and TIICs have been widely reported. Kaur et al 20 marked the T cells in PCa tissues with CD3, CD8, and FOXP3 immunostaining and revealed that ERG activity and PTEN loss were affected by the high proportion of T cells, but clinical outcomes showed no association with these results. Petitprez et al 21 reported that a high proportion of CD8 + T cells could lead to a greater risk of advanced development of PCa patients with node metastasis.…”

The adequacy of tissue microarrays in the assessment of inter- and intra-tumoural heterogeneity of infiltrating lymphocyte burden in leiomyosarcoma

“…Intra-tumoural heterogeneity in the immune microenvironment has been described in numerous epithelial cancer types, both within primary lesions and between different metastatic sites 7,[11][12][13][14][15] . In breast cancer, a vTMA methodology was used to demonstrate that agreement between TMA and whole tumour assessment of TIL burden plateaued when sampling any more than four 0.6mm cores 23 .…”

“…It is now known that the presence or absence of immunerelated factors such as tumour-infiltrating lymphocytes (TIL) can serve as powerful prognostic and/or predictive biomarkers across a range of cancer types [7][8][9][10] . TMAs continue to be frequently employed in studies that seek to investigate the potential role of TILs as putative biomarkers 7,[11][12][13][14][15] . The success of such studies is dependent on the ability of the TMA approach to capture a sufficiently representative picture of the immune phenotypes present within the wider tumour.…”

Caracterização do genoma e da resposta imune no microambiente tumoral de neoplasias PTEN-deficientes

“…The most novel finding from this study is that PTEN-deficient prostate tumors exhibited increased IDO1 protein expression and had higher FoxP3+ Treg density, suggesting expansion of immunosuppressive factors in PTEN-deficient prostate cancer 159,160 . Although mechanistic studies are needed to assign causal associations, it can be A study conducted on 312 primary prostate cancer specimens showed that high FoxP3+ Treg cell density was not associated with clinicopathological features but was significantly associated with earlier biochemical recurrence and prostate cancer metastasis 81 .…”

“…The immune-cell landscape of tumors that harbor PTEN somatic mutations is complex and highly heterogeneous, with studies showing that PTEN deficiency is linked to high CD8+ T-cell density 66,81 while others exhibit inverse correlations with this cell type [82][83][84] (Table 1).…”