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With the rapid development of cancer immunology, more and more research focuses on the role of immune cells and signaling molecules in the tumor microenvironment. Prostate cancer is the second most common malignant tumor in men globally. With the increase in our population ages and screening rates, the incidence of prostate cancer in China is increasing. Androgen deprivation therapy (ADT) is a primary treatment for late-stage prostate cancer. However, most patients eventually progress to castration-resistant prostate cancer (CRPC) after ADT treatment. The median survival of CRPC patients has been less than two years. Although new treatment methods have emerged in recent years, and patient survival has improved, however, the overall prognosis still remains poor. Tumor immunotherapy works by stimulating or rebuilding the body's immune system to control and kill tumor cells. In recent years, immunotherapy has entered clinical research and rapidly developed into an effective tumor-treatment approach following surgery, radiotherapy, chemotherapy and targeted therapy. However, the effect of immunotherapy on CRPC patients is usually very poor. Therefore, the tumor microenvironment of CRPC has attracted many scholars' attention. Previous studies have suggested that CRPC generally has less immune infiltration, a relatively high immunosuppressive tumor microenvironment, such as low infiltration and activity of T cells, and high expressions of various immunosuppressive factors, such as cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1), etc., which is considered as an immune "cold" tumor. In addition to its own immune-inhibitory mechanisms, CRPC has complex immune evasion mechanisms that suppress immune cell activity or selectively express low immunogenic antigen to evade immune system recognition. Due to the particular immunosuppressive tumor microenvironment of CRPC, the effect of immunotherapy alone is often unsatisfactory. Therefore, the selection of appropriate immunotherapy strategies has become the key to improving the treatment effect of CRPC patients. This review summarized the mechanisms underlying immune cells in the immune microenvironment of CRPC tumors and their interactions with various cytokines in the context of immune checkpoint inhibitor therapy combined with ADT, chemotherapy, Sipuleucel-T tumor vaccines, chimeric antigen receptor-T (CAR-T) cell therapy, oncolytic virus therapy, or in combination with chemokine receptor antagonists, tyrosine kinase inhibitors, poly (ADP-ribose) polymerase (PARP) inhibitors and other treatments. In conclusion, the tumor immune microenvironment of CRPC is highly complex, and immunotherapy still faces many challenges. However, with the progress of technological advancements and research, some new immunotherapy options are being studied, and it is believed that tumor immunotherapy will bring better therapeutic effects to patients with CRPC in the future.

Tip-enhanced Raman spectroscopy (TERS) has recently been developed to push the spatial resolution down to single-chemical-bond scale. The morphology of the scanning tip, especially the atomistic protrusion at the tip apex, plays an essential role in obtaining both high spatial resolution and large field enhancement at the Ångström level. Although it is very difficult to directly characterize the atomistic structures of the tip, the Raman scattering from the apex’s own vibrations of the metal tip can provide valuable information about the stacking of atoms at the tip apex. However, conventional quantum chemistry packages can only simulate the Raman scattering of small metal clusters with few atoms due to huge computational cost, which is not enough since the shaft of the tip behind the apex also makes significant contributions to the polarizabilities of the whole tip. Here we propose an atomistic polarization model to simulate the Raman spectra of large metal tips at subwavelength scales based on the combination of the atomistic discrete dipole approximation model and the density functional theory. The atomistic tip with different sizes and stacking structures is considered in its entirety during the calculation of polarizabilities, and only the vibrational contributions from the tip apex are taken into account to simulate the Raman spectra of the tip. The Raman spectral features are found to be very sensitive to the local constituent element at the tip apex, atomic stacking modes, and shape of the tip apex, which can thus be used as a fingerprint to identify different atomistic structures of the tip apex. Moreover, our approaches can be extended to the metal tips with sub-wavelength sizes, making it possible to consider both the large scale and the atomistic detail of the tip simultaneously. The method presented here can be used as a basic tool to simulate the Raman scattering process of the metal tips and other nanostructures in an economic way, which is beneficial for understanding the roles of atomistic structures in tip- and surface-enhanced spectroscopies.