Abstract:
Prostate cancer stands as a prominent malignancy of the prostate gland, a
leading cause of male mortality globally. This cancerous growth disrupts the pro-
duction of prostatic fluid, integral for sperm transportation and safeguarding. Pro-
gression of this cancer is steered by flawed cell signaling, immune response and
gene expression, ultimately enabling evasion, expansion, and metastasis. Conven-
tional treatments often spur drug resistance and a more aggressive cancer phenotype.
This study utilized bulk and single-cell RNA-sequencing techniques to delve into
the fundamental molecular and cellular changes underpinning prostate cancer with
focus towards immune response from both tumor and normal prostate glands. Out-
comes spotlighted 1,634 differentially expressed genes, notably introducing novel
noncoding (SCARNA3, SNORA74D, SNORD70) and coding (MSTRG.11932.6,
MSTRG.28256.4, MSTRG.25472.3) alternatively spliced transcripts involved in im-
mune responses and crosstalk. Furthermore, detailed scrutiny at the single-cell level
unveiled dampened anti-tumor pathways, such as TCR and MHC-II, spanning various
immune cell categories, thus signifying a compromised tumor microenvironment from
an immunological standpoint. Conversely, pathways propelling tumor advancement,
including interleukins, maintained consistent elevation, fostering prolonged inflam-
mation that propels tumor growth while circumventing immune vigilance. Cell-cell
communication analysis revealed the role of IL-2 and IL-4 pathways in nurturing
immunosuppression within the tumor microenvironment through T-cell anergy, fa-
cilitated through CD4+ NKT-like, CD8+ NKT-like and memory CD4+ cells. This
comprehensive approach further pinpointed the disruption of key signaling molecules
(IL2RG, IL2RB, IL7R), involved in IL-2 and IL-4 pathways inhibited essential im-
mune response pathways, such as TCR and MHC-II antigen presentation, crucial for
anti-cancer activities. This study identifies novel (IL2RB, IL2RG) cancer immunother-
apy targets for targeted immunotherapy against prostate cancer.
