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effect profile, reduced disease progression in patients with metastatic CRPC, and improved PFS. The
trial also indicated that TASQ exerted antiangiogenic and antimetastatic effects by altering MDSC
activity in the tumor microenvironment [53-56] . Utilizing activated T cells (aATCs) that are equipped
with bispecific antibodies (Bi) against tumor antigens like Her2 or EGFR has been demonstrated to
increase the antitumor effects of immunotherapy. Additionally, to directly destroy tumor cells, these
aATCs can lower the quantity and activity of myeloid-derived suppressor cells (MDSCs), which are
immune cells that block the antitumor immune response. The expression of enzymes like COX2, PGE2,
and ARG1 that mediate the suppressive function of MDSCs can be inhibited by aATCs. Additionally,
aATCs have the ability to create cytokines and chemokines such as IL-2, IFN-, CXCL9, and CXCL10
that aid in the attraction and activation of other immune cells. Consequently, this approach can
concurrently target tumor cells and MDSCs, which will improve the final outcome of immunotherapy .
[57]

Tumor microenvironment modulation to enhance immune-based therapies
Tumors can employ a variety of tactics to avoid immune attack and establish a tolerant microenvironment.
These tactics include reducing antigen presentation, activating unfavorable costimulatory signals, creating
immunosuppressive substances, enlisting regulatory cells, etc. These mechanisms can inhibit the activity
and function of different types of immune cells, including dendritic cells, natural killer cells, and T cells. The
presence of negative costimulatory ligands such as PDL-1 and CTLA-4, along with regulatory lymphocytes
and myeloid cells, as well as tumor-derived factors such as IL-10, transforming growth factor-β (TGF-β),
and IDO, presents challenges for effectiveness of immune-therapy and antitumor actions [58,59] . To overcome
these challenges, combining vaccines with therapeutic approaches designed to counteract the immune-
suppressive microenvironment, like using imatinib (to inhibit IDO), sunitinib (to counteract MDSCs and
Treg cells), cyclophosphamide (to eliminate Treg cells), gemcitabine (to eliminate MDSCs), can increase the
impact of immunotherapy, bolster antitumor immune responses [60-63] .

T-regulatory and T-17 cells
Tregs are immune cells that suppress the immune response to self-antigens and tumors, while Th17 cells are
immune cells that produce a pro-inflammatory cytokine called IL-17. Peripheral tolerance to self-antigens is
regulated by Tregs, constituting 5%-10% peripheral CD4+ T cells. Treg deficiency can lead to
autoimmune responses, and these cells play a crucial role in dampening the immune system's
response to cancers, thereby facilitating tumor growth. Enhanced immune suppression in prostate
cancer patients is linked to tumor development. Following androgen ablation, an increase in Tregs might
contribute to the temporary immune response. Studies comparing pre- and post-vaccination patients
revealed a correlation of P = 0.029, within overall survival (OS), and a decrease in Treg suppressive
activity [64-68] . Prostate cancer patients undergoing active whole-cell immunotherapy displayed an inverse
relationship between progression-free survival (TTP) and the frequency of CCR4/IL-17/CD4+ T cells
before immunization. Responders had Th17 profiles similar to healthy controls, differing significantly
from non-responders. In mice with endogenous prostate cancers, adding less dose of cyclophosphamide
to cell-based immunotherapy enhanced treatment effectiveness by modulating Teff/Treg ratios,
suppressing Tregs and boosting effector T cells. FLII, controlling PD-L1 expression via the YBX1
signaling axis, is vital in enzalutamide-resistant CRPC. Inhibiting this pathway synergistically
enhanced CRPC treatment, reducing Tregs and MDSCs while promoting CD8 T cell proliferation.
These findings support targeted therapy for endocrine therapy-resistant CRPC, utilizing the functional link
between signaling pathways of FLII, YBX1/PD-L1 [69-71] .

TARGETS FOR PROSTATE CANCER IMMUNOTHERAPY
Various forms of immunotherapy are available for treating prostate cancer. The following are some
immunotherapy targets for prostate cancer [Figure 2].