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Racial differences in prostate tumor 
microenvironment: implications for 
disparate clinical outcomes and 
potential opportunities 
 

Sandeep Goswami 1,2  Chandrani Sarkar 1, 2,3,  Seema Singh 1, 2,3 Ajay Pratap Singh 1,2,3  Debanjan 
Chakroborty 1,2,3 

1 Department of Pathology, University of South Alabama, Mobile, Alabama, USA. 
2 Cancer Biology Program, Mitchell Cancer Institute, University of South Alabama, Mobile, Alabama, USA. 
3 Department of Biochemistry and Molecular Biology, University of South Alabama, Mobile, Alabama, USA. 

*Corresponding author: Debanjan Chakroborty, Email: dchakroborty@southalabama.edu,  

 

 

ABSTRACT 
Disparities in cancer incidence and outcome are common among the racial and ethnical minorities in the 
United States and are of significant social and clinical concern. Prostate cancer is the most commonly 
diagnosed non-cutaneous malignancy in American men and exhibits substantial racial disparities with 
African American men bearing the highest burden in terms of incidence and mortality. A multitude of 
factors, including socioeconomic, behavioral, and access to healthcare, have been implicated as the 
underlying causes of such disparities. More recent data also suggest that there are inherent molecular 
and biological differences in prostate tumors of patients having distinct racial backgrounds. Tumor 
microenvironment has tremendous impact on the course of cancer progression and clinical outcome and 
may also contribute to the racial disparities observed in prostate cancer. Therefore, a better understanding 
of critical differences in the tumor microenvironment components may provide newer directions to study 
the biological causes of prostate cancer health disparities and may identify novel therapeutic targets. This 
review discusses the findings related to the tumor microenvironment differences between African 
American and Caucasian American prostate cancer patients and makes suggestion regarding their 
potential significance in prostate cancer disparities. 

KEYWORDS: Prostate cancer, racial disparity, tumor microenvironment 

Citation: Goswami S et al (2022) Racial differences in prostate tumor microenvironment: implications for 
disparate clinical outcomes and potential opportunities. Cancer Health Disparities. 6: e1-e14. 
doi:10.9777/chd.2022.1003 



 
 
 
 
 

 
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1.0. Introduction 
Prostate cancer (PCa) is the most commonly 
diagnosed non-cutaneous malignancy and the 
second leading cause of cancer-related death in 
American men [1, 2]. Among all the cancers, PCa not 
only shows extreme variations in its potential to cause 
morbidity and death in men but also displays great 
variations in geographic and racial distribution [1, 2, 3, 
4]. In the United States, despite significant 
improvements in cancer diagnosis and treatment 
strategies, African American (AA) men suffer 
disproportionately from PCa with over 80% higher 
incidence rates than men of European American (CA, 
Caucasian American) origin [5, 6, 7, 8]. AA men are 
also more likely to be diagnosed at a younger age and 
present with more advanced and aggressive disease 
stages [8-12] compared to men with CA ancestry. 
Accordingly, for AA men, the lifetime risk of 
developing PCa is 1 in 6, while that for CA men is 1 in 
8. AA men are also greater than twice as likely to 
succumb to the disease compared with CA men as 
the PCa specific mortality in AA men is 1 in 23 whereas 
it is 1 in 42 in CA men [1, 2, 7]. 

In order to overcome the disparity that affects AA 
population negatively and to develop personalized 
therapeutic approaches, we need to identify and 
understand the factors that drive PCa tumor 
progression and metastasis in AA men. Over the 
years, a number of such interconnected factors 
including socioeconomic status, lifestyle and dietary 

issues, problems with accessing healthcare have 
been identified as probable causes of this 
epidemiological disparity in PCa incidence and 
mortality [1, 2, 8]. Interestingly, several newer lines 
of evidence have also demonstrated genetic and 
biological variations among patients of different 
racial backgrounds. The androgen hormonal axis, 
the androgen receptor (AR), and its signaling 
pathway play critical roles in PCa progression 
[13].Several aspects of the AR pathway have also 
been implicated in PCa associated racial differences 
[14-16]. However, in addition to androgens and AR 
signaling, the crosstalk between epithelial cells and 
cellular components of the tumor 
microenvironment (TME), such as mesenchymal 
stem cells, endothelial cells, 
fibroblasts/myofibroblasts, and immune cells also 
plays an integral role in PCa progression and 
metastasis [2,17]. The immune cells as well as the 
endothelial cells forming the blood vessels in the 
PCa TME, secrete growth factors and cytokines to 
induce PCa cell proliferation and spread [2, 17]. 
Increasing evidences now indicate that the TME 
components may also be a significant contributor 
to the racial disparity observed in PCa incidence, 
aggressiveness and clinical outcomes between AA 
and CA populations [2, 18-20]. Therefore, we have 
reviewed the pertinent data to discuss the potential 
contribution of the TME to the observed racial 
disparity associated with PCa (Table 1). 

 
 
 
 
 
 
 
 
 



 
 
 
 
 

 
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Table 1. Role of stromal cells in AA and CA PCa. 

Cell type Role in PCa Differences in AA and CA PCa References 

Fibroblasts  • Secrete chemokines, cytokines, 
growth factors (brain derived 
neurotrophic factor and 
chemokines like CCL5, CXCL5, 
SDF1-alpha and soluble factors 
such as VEGF, bFGF, HGF) 

• Promote tumor growth and 
metastasis  

• Pro-inflammatory cytokines and growth 
factors [brain-derived neurotrophic factor 
(BDNF), VEGF, and fibroblast growth factor 7 
(FGF7)] are significantly elevated in AA PCa 

• Higher expressions of myofibroblast 
activating markers [αSMA, vimentin, and 
FAP1] and mesenchymal stem cell marker, 
CD90, in cancer associated fibroblasts (CAFs) 
of AA PCa 

2,19 

Immune cells • Inflammation promotes initiation 
and progression 

• Increased lymphocytic infiltration in AA PCa 
tissues 

• Pro-inflammatory cytokines (interferon-alpha 
(IFNα), IFNγ, tumor necrosis factor-alpha 
(TNFα), and Interleukin 4 and Interleukin 13) 
are upregulated in PCa of AA men 

• Increased NK cell activity in AA PCa 

2, 28, 34-36 

Endothelial 
Cells 

• Form neovesels to support tumor 
growth and metastatic 
progression 

• Increased VEGF secretion in AA PCa 
• Higher MVD in AA PCa tissues 

2,19, 44, 50 

 
2.0. Prostate Cancer Microenvironment 
Prostate, a tubule-alveolar gland is primarily 
composed of prostatic epithelial cells surrounded 
by the stromal components [17, 21]. The gland has 
three distinct zones; peripheral, central, transition, 
and a mixed zone called the anterior fibro-muscular 
zone or stromal zone [17, 21, 22]. It is mainly 
composed of four major epithelial cell types- basal 
cells, neuroendocrine cells, epithelial 
stem/progenitor cells, and secretory luminal cells 
[17, 22]. The stroma consists primarily of fibroblasts, 
myofibroblasts, endothelial cells, immune cells, 
nerve cells and smooth muscle cells [17, 22]. 

The development and progression of PCa is a 
complex process and the disease is extremely 
heterogeneous from molecular, cellular and clinical 
standpoints [23]. In most cases, PCa originates in 
prostatic epithelial cells. Therefore, studies on PCa 

development and progression have mainly focused 
on these cells [22, 23]. However, epithelial cells are 
not sole players contributing to PCa tumorigenesis; 
the stromal cells in the TME also play critical roles in 
PCa development and progression [2, 17, 24]. The 
crosstalk between the stroma and the epithelium is 
a major driver of PCa pathogenesis and disease 
progression [24, 25]. The interaction between the 
epithelial or cancer cells and the non-epithelial or 
stromal cells in PCa is mediated by a variety of 
paracrine factors secreted both by cancer cells as 
well as by the stromal cells [2, 25] (Figure 1). Several 
studies have emphasized the contribution of 
altered/reactive stromal microenvironment 
characterized by increase in the numbers of 
myofibroblasts and fibroblasts and significant 
decrease in the numbers of smooth muscle cells in 
tumorigenesis and progression of PCa [17, 25]. 



 
 
 
 
 

 
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Figure 1: Interaction between PCa cells and the stroma (Created by BioRender) 

 
 
Regarding the disproportionate burdens of PCa 
between AA and CA populations, while most 
studies have focused on genetic differences within 
different prostate tumor subtypes, emphasizing 
mostly on PCa cells, a handful of studies have also 
indicated how differences in PCa TME can affect 
tumor progression among men with different racial 
and ethnic backgrounds [18, 19]. Altered gene 
expression profiles of fibroblasts, immune cells and 
angiogenic components was noted between the 
TME of AA and CA men with PCa [18-20, 26-27]. In 
a study involving PCa samples from patients of AA 
and CA backgrounds, a total of 677 genes 
associated with 103 pathways were identified to be 
differentially expressed in the PCa TME [20]. 
Furthermore, pathway analysis and disease 
association studies have revealed a significant 

difference in tumor inflammatory response and 
cytokine secretion between AA and CA patient 
samples [18, 20, 21, 28, 29].The differences in TME 
of AA and CA PCa patients may account for the 
differences observed in tumor growth, progression 
and therapeutic response. In the following sections, 
we will therefore discuss the racial differences 
observed in three important cellular components of 
the TME in PCa: cancer associated fibroblasts 
(CAFs), immune cells and endothelial cells. 

2.1. Fibroblasts 
The stromal fibroblasts play a major role in normal 
prostate development as well as in PCa progression 
[2, 17, 25]. Cancer associated fibroblasts (CAFs) form 
a major component of TME and they actively 
communicate with PCa cells both via direct contact 



 
 
 
 
 

 
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and via soluble mediators such as chemokines, 
cytokines, growth factors secreted by both of the 
cell types [2, 17, 25, 30, 31]. This bidirectional 
communication between PCa cells and CAFs is 
crucial for tumor progression and metastasis. CAFs 
secrete growth factors like brain derived 
neurotrophic factor and chemokines like CCL5, 
CXCL5, SDF1-alpha and soluble factors such as 
VEGF, bFGF, HGF that promote PCa growth and 
progression [2, 19]. Studies have shown CAFs can 
differentially impact PCa progression in AA and CA 
patients. In a study where prostate fibroblasts from 
PCa specimens of AA and CA patients with similar 
clinicopathologic characteristics were isolated, it 
was noted that pro-inflammatory cytokines and 
growth factors [brain-derived neurotrophic factor 
(BDNF), VEGF, and fibroblast growth factor 7 
(FGF7)] were significantly elevated in CAF isolated 
from AA PCa samples compared to CA PCa [19]. In 
addition, myofibroblast activating markers [αSMA, 
vimentin, and FAP1] and mesenchymal stem cell 
marker, CD90, showed significantly higher 
expressions in AA CAFs compared with CA CAFs 
[19]. With increased myofibroblastic components 
and presence of a population of mesenchymal-like 
cells (CD90+) it was inferred that AA-derived cells 
would show increased response to growth factors 
compared with CA-derived cells [19]. On the other 
hand, the expression of Caveolin1 (CAV1) that is a 
membrane-associated protein , whose expression 
in cancer cells increases with progression but loss in 
PCa stroma correlates with reduced relapse-free 
survival [19, 32, 33], was found to be lower in AA 
CAFs compared with CA CAFs. Upon exposure of 
PCa cells to conditioned media from fibroblasts 
isolated from AA and CA PCa patients, it was seen 
that there was increased proliferation and migration 
in vitro when PCa cells were exposed to conditioned 
media from AA prostate fibroblasts compared to 
CA prostate fibroblasts [19]. Furthermore, this study 
demonstrated that regardless of the racial 

background of PCa cells, growth and/or 
proliferation of PCa cells was significantly increased 
when conditioned media from AA patients’ 
fibroblasts was used (19). In addition, the study also 
reported an increased collagen deposition and 
myofibroblasts forming the ‘reactive stroma’ and 
elevated expression of fibroblast specific marker, 
tenascin-C, in the extracellular matrix (ECM) of AA 
PCa patients [19]. High expression of tenascin-C in 
CAFs is associated with poor prognosis in PCa 
[34].Taken together; these data suggest that CAFs 
in AA PCa patients produce significantly higher 
levels of growth factors that enhance the 
tumorigenicity of PCa cells compared with CAFs in 
CA PCa patients. 

2.2. Immune Cells 
Although PCa is considered as a poorly 
immunogenic tumor, chronic inflammation has 
been consistently shown to be associated with the 
development and progression of the disease [35]. 
Immune cells form the cellular arm of inflammatory 
responses and presence of inflammatory cells in 
PCa TME is well documented.Only a few studies 
however have explored the immunological 
differences observed in the TME of AA and CA 
PCa.[36]. Very recently, it was reported that there is 
over-representation of immunogenic TME in AA 
PCa patients, with significantly higher inflammatory 
cytokines and lymphocytic infiltrates which 
increases the potential for better response to 
immunotherapy in these patients [37] . Studies have 
reported a significant difference in both the 
numbers and types of inflammatory cells and 
inflammatory responses between AA and CA PCa 
populations. Differences were noted between AA 
and CA PCa patients in expression of chronic 
inflammatory cytokines, such as interferon-alpha 
(IFNα), IFNγ, tumor necrosis factor-alpha (TNFα), 
Interleukin (IL) IL-1β, IL 4, IL 6, IL 8 and IL 13. These 
pro-inflammatory cytokines show significant 



 
 
 
 
 

 
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upregulation in PCa of AA men [20, 38]. IL-6 
promotes migration of cells and helps to evade 
apoptosis through STAT and PI3K pathways and is 
considered immunosuppressive as it helps to recruit 
myeloid derived suppressor cells (MDSC) to the 
TME [37, 39]. IL-8 activates neutrophil and plays a 
role in cell proliferation and invasion. Higher levels 
of IL-8 expression in PCa was associated with higher 
tumor grade but this association was comparable in 
AA and CA PCa [37, 40]. A recent study that was 
conducted using grade, stage matched AA and CA 
PCa, has reported an increased lymphocytic 
infiltration in AA PCa tissues compared to PCa 
tissues of CA origin [28]. Upon further analysis of 
the lymphocytic population, the study reported a 
higher presence of plasma cells in TME of AA PCa 
that correlated with IFNγ expression and increased 
inflammation observed in these tissues [28]. High 
expression of IgG was also noted in these AA PCa 
samples, which suggested more antibody secretion 
by these cells [28]. In addition, increased activity of 
NK cells, which primarily drives antibody dependent 
cellular toxicity, have been reported in AA PCa 
tissues compared to tissues from CA patient [28]. A 
different study also reported that AA PCa had 
higher expression of CD4+ and CD8+ T-cell 
markers in TME [38]. In contrast, there is also a 
report that indicated no difference in T-cell 
infiltration between AA and CA PCa but increased 
regulatory T-cells in AA PCa that correlated with 
disease recurrence [41]. Poor disease prognosis 

associated with lymphocytic TME infiltrates may be 
due to their association with more aggressive 
tumors, or as the infiltrating T-cells were 
dysfunctional, or as were immunosuppressive 
regulatory T-cells [37, 42]. 

Macrophages comprise a major portion of the 
immune cells in the TME. M1 type or classically 
activated macrophages which are anti-tumorigenic 
and M2 type or alternatively activated 
macrophages which are pro-tumorigenic have 
been shown to be present in the PCa TME. In the 
TME, the tumor-associated macrophages (TAMs) 
are converted from a M1-type to the M2-type 
phenotype that secrete numerous growth factors, 
which influence diverse processes during PCa 
progression.The density and type of TAMs present 
in PCa thus provide prognostic information [2, 43]. 
AA PCa patients show increased TAM numbers 
compared to CA PCa patients as both CD68+ (M1), 
and CD163+ (M2) cells were significantly higher in 
AA PCa tissues [2]. 

A study investigating the role of inflammation and 
immune genes in AA PCa characterized 124 TME 
and immune response genes in AA PCa patients 
[44]. It was reported that 22% of total AAM patients 
showed adverse pathology features, high genomic 
risk (53%) and higher expressions of immune-
response genes some of which along with their 
functions have been included in Table 2. 

 

Table 2: Immune response genes elevated in AA PCa patients compared to CA PCa patients. 

Gene Name Expression in 
AA PCa patients 

Role in cancer References 

Cluster of 
differentiation 2 (CD2)  

Immunomodulatory in the TME; associated with 
delayed disease progression; enhances tumor 
immunogenicity and may improve response to 
immunotherapy. 

44, 45 



 
 
 
 
 

 
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Cluster of 
differentiation 3 (CD3) 

 
 

Activates cytotoxic T cells (CD8+ naive T cells) and 
T helper cells (CD4+ naive T cells). 

44, 46 

Cluster of 
differentiation 4 (CD4) 

 
 

Immunosuppressive; may help in identifying patient 
subset that would benefit from immunotherapy. 

44, 47, 48 

Cluster of 
differentiation 45 
(CD45) 

 
Regulates lymphocyte survival, cytokine responses, 
and TCR signaling; altered CD45 could result in 
severe combined immunodeficiency. 

44, 49 

Cluster of 
differentiation 96 
(CD96) 

 
Inhibits function of CD8+ T cells; regulates NK cell 
effector function and cellular metastasis. 

44, 50 

C-C Motif Chemokine 
Ligand 5 (CCL5) 

 
 

Promotes angiogenesis and metastasis; increases 
drug resistance; promotes self-renewal of PCa cells. 

44, 51 

C-X-C Motif 
Chemokine Ligand 9 
(CXCL9) 

 
Inhibits cytokine secretion from T cells; promotes 
PCa progression.  

44, 52 

C-X-C Motif 
Chemokine Ligand 10 
(CXCL10) 

 
Increase infiltration of pre-adipocytes and TAMs in 
PCa TME; promotes migration and invasion of PCa 
cells. 

44, 53 

C-X-C Motif 
Chemokine Ligand 11 
(CXCL11) 

 
Promotes PCa cell migration and invasion. 44, 54 

Signal transducer and 
activator of 
transcription 1 (STAT1) 

 
Tumor suppressor in early PCa stages; promotes 
drug resistance. 

44, 55 

Indoleamine 2,3-
dioxygenase 1(IDO1) 

 
 

Mediates immunosuppression; associated with 
significantly worse clinical outcomes. 

44,56 

Matrix 
metallopeptidase 9 
(MMP9) 

 
Promotes angiogenesis. 18, 57 

Autocrine motility 
factor receptor (AMFR) 

 
 

Mediates AMF-mediated cell migration and 
metastasis. 

18, 58 

 
Taken together, the TME in PCa exhibits an 
immunosuppressive microenvironment and 
manifests a unique immune repertoire in AA 
population characterized by increased 
inflammatory mediators and significant enrichment 
of proinflammatory immune pathways creating a 
tumor supportive environment that negatively 

associates with disease outcomes. However, a study  
also indicates that there is no significant association 
between inflammatory infiltrate and inflammation 
and  the difference in PCa incidence and outcomes 
in different racial groups [59, 60].Therefore, more 
studies are needed to draw a conclusion regarding 



 
 
 
 
 

 
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contribution of immune microenvironment to PCa 
associated racial disparity. 

2.3. Endothelial Cells 
In addition to the fibroblasts and immune cells, 
endothelial cells form a major cellular component 
of the TME. Endothelial cells form new blood vessels 
from existing vasculature by a process termed 
angiogenesis to meet the nutrient and oxygen 
requirements of the rapidly dividing cancer cells. 
Additionally, these cells by forming neovessels 
provide routes for dissemination of cancer cells to 
other parts of the body [61-67]. In order to 
propagate and form new blood vessels the 
endothelial cells in TME respond to growth factors 
secreted by cancer cells and cells in TME including 
endothelial cells themselves , such as vascular 
endothelial growth factor (VEGF) and fibroblast 
growth factor (FGF). PCa, like other solid tumors 
depends on angiogenesis and overexpression of 
proangiogenic factors like VEGF and FGF have been 
shown to be associated with poor PCa prognosis 
[65, 68-71]. 

VEGF is the most prominent cytokine regulating the 
process of angiogenesis [65, 70, 72, 73 ]. In PCa, the 
expressions of VEGF and/or its receptor VEGFR-2 
are directly correlated to tumor Gleason grade, 
metastatic potential, and progression-free survival 
(PFS). In AA PCa TME increased VEGF secretion by 
fibroblasts may impact tumor angiogenesis [71]. 
Microvessel density (MVD) a surrogate marker 
assessing angiogenic response in tissues has been 
shown be higher in PCa tissues collected from AA 
patients compared to patients with CA background. 
[2, 19]. These differences in expression of 
angiogenic factors and angiogenic response 
observed between PCa of AA and CA men could 
differentially influence PCa growth, metastasis and 
clinical outcomes in these two populations. 

3.0. Clinical implications of the racially 
different tumor microenvironment 
composition in prostate cancer 
TME in PCa patients with different racial 
backgrounds show prominent genetic variability 
which influences their ability to synthesize, secrete 
and, respond to growth factors which results in 
differential growth, progression and therapeutic 
responses [2, 17, 19, 20, 24]. With the differences 
observed in TME, it is more likely that AA PCa 
patients may respond differently to different 
therapeutic strategies. Recent evidence indicates 
that even though immunotherapy has not been 
very successful in PCa, AA patients might benefit 
from it due to the differences in the immune 
landscape. In the PROCEED (NCT01306890) trial for 
receiving immunotherapy with sipuleucel-T for 
metastatic castration resistant prostate cancer 
(mCRPC), AA PCa patients showed a higher survival 
advantage than CA PCa patients [74]. In the PSA-
matched set, median overall survival (OS) for AA 
patients was 35.3 and that for CA patients was 25.8 
months and in the all patient set, OS of AA patients 
was 35.2 monthsas compared to 29.9 months for 
CA patients. mCRPC AA patients with lower 
baseline PSA showed even longer OS of over 4.5 
years compared to 2.8 years for CA patients. The 
better response to immunotherapy shown by AA 
PCa patients proves the differences in immune 
response in AA and CA PCa patients [35]. AA PCa 
patients have been predicted to have higher 
response score to DNA damage and alkylating 
agent-based chemotherapy whereas CA PCa has a 
higher response score to microtubule-based 
chemotherapy [44]. Other studies have reported 
that the regular use of aspirin can significantly 
reduce both the risk of developing metastatic PCa 
and disease recurrence in AAM [75, 76] by targeting 
the pro-inflammatory cyclooxygenase/ 
thromboxane A2 pathway [77]. Evidence also 
suggests reduced mortality due to PCa in AAM 



 
 
 
 
 

 
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using aspirin [78].Furthermore, TME facilitates 
therapeutic resistance by modification of stromal 
components to promote invasion, angiogenesis, 
and metastases. Patient response to therapy 
depends strongly on activation of tumor stroma. 
The presence of myofibroblasts, that show higher 
expressions in AA patients than CA patients, 
predicts biochemical recurrence in PCa patients 
[79]. CAFs were also shown to induce 
chemoresistance through induction of EMT [80]. 
Interaction of TAMs and cancer stem cells (CSCs) 
can result in resistance to ADT therapy. CSCs help 
in TAM remodeling and TAMs promote the stem-
like properties of CSCs and drug resistance by 
acting through the IL-6/STAT3 signaling pathway 
[81]. 

4.0. Conclusion and future perspective 
The TME is a key contributor to PCa progression 
and determinant of clinical outcomes. The stromal 
cells and the extracellular milieu of the TME regulate 
the plasticity of the phenotypic traits of PCa cells. 
The interaction between PCa cells and surrounding 
TME components (immune, vascular, and stromal) 
are therefore being studied extensively to 
understand its broader role in pathobiology and 
disease outcomes [2, 17, 19, 20, 24] using traditional 
in vitro and in vivo experiments and recently by 
fluorescence-activated cell sorting or laser 
microdissection with RNA sequencing and spatial 
transcriptomics [82, 83, 84]. The recent technique 
of multiplex immunofluorescence (mIF) with 
tyramide signal amplification helps to gather 
maximum information from a single tissue section 
with accurate classification of the TME cell 
population [85]. Use of single-cell RNA 
transcriptome sequencing (scRNA-seq) can indicate 
the cell heterogeneity and help to analyze cellular 
interactions [82]. The use of these techniques will 
further help to identify the role of the modulated 

genes in individual TME components of AA and CA 
PCa. 

Data related to the role of TME in race-associated 
cancer health disparity has only recently begun to 
emerge in prostate and other cancers. Further 
studies involving larger datasets from diverse 
patient populations would provide more strengths 
to TME differences and their association with clinical 
outcomes and clinicopathologic progression of 
cancer. Similarly, more efforts should also be made 
to determine the exact contribution of TME to 
differential PCa progression using appropriate 
experimental models and delineate the underlying 
molecular mechanisms. Unlike the cancer cells, cells 
of the TME are genetically stable, which make them 
attractive targets for cancer management 
(prevention and treatment) and to reduce the risk 
of acquiring therapy resistance leading to treatment 
failure and recurrence. A better understanding of 
the role of the TME will also help in the 
development of race-specific biomarkers and 
therapeutic targets leading to personalized 
approaches for risk prediction, diagnosis, 
monitoring, and management of PCa. 

Acknowledgments 
Authors are supported by funding from NIH/NCI 
(R01CA231925 to SS) and USA Health Mitchell 
Cancer Institute, University of South Alabama. 

Conflicts of interest 
The authors declare that they have no conflicts of 
interest with the contents of this article. 

Authors’ contributions 
Conception and design: DC. Initial 
manuscript writing: SG, CS, and DC. 
Review and revision of the manuscript: 
SG, CS, SS, APS and DC. 
 



 
 
 
 
 

 
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	1.0. Introduction
	2.0. Prostate Cancer Microenvironment
	2.1. Fibroblasts
	2.2. Immune Cells
	2.3. Endothelial Cells

	3.0. Clinical implications of the racially different tumor microenvironment composition in prostate cancer
	4.0. Conclusion and future perspective
	Acknowledgments
	Conflicts of interest
	Authors’ contributions

