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With the rapid advancement of imaging equipment and minimally invasive technology, cryoablation technology is being used more frequently in minimally invasive treatment of tumors, primarily for patients with early tumors who voluntarily consent to ablation as well as those with advanced tumors that cannot be surgically removed or cannot be tolerated. Cryoablation is more effective and secure for target lesions than other thermal ablation methods like microwave and radiofrequency ablation (RFA). The study also discovered that cryoablation, in addition to causing tumor tissue necrosis and apoptosis, can facilitate the release of tumor-derived autoantigens into the bloodstream and activate the host immune system to elicit beneficial anti-tumor immunological responses against primary. This may result in regression of the primary tumor and distant metastasis. The additional effect called “ Accompanying effects “. It is the basis of combined ablation and immunotherapy for tumor. At present, there is a lot of research on the mechanism of immune response induced by cryoablation. Trying to solve the question: how positively induce immune response. In this review, we focus on: 1. the immune effects induced by cryoablation. 2. the effect and mechanism of tumor immunotherapy combined with cryoablation. 3.The clinical research of this combination therapy in the treatment of tumors.

This article reports a case of a large intracranial arachnoid cyst in a soldier who had performed well. This is a very marvelous and interesting case. Although the cyst pressed the entire brain into the contralateral cranial cavity, the patient did not show any significant clinical symptoms and had excellent motor and cognitive abilities, reflecting the excellent plasticity of the brain tissue.

Chemical ablation was designed to inject chemical agents directly into solid tumors to kill cells and is currently only used clinically for the palliative treatment of tumors. The application and combination of different drugs, from anhydrous ethanol, and glacial acetic acid to epi-amycin, have been clinically tested for a long time. The effectiveness is unsatisfactory due to chemical agents’ poor diffusion and concentration. Immunotherapy is considered a prospective oncologic therapeutic. Still, the clinical applications were limited by the low response rate of patients to immune drugs and the immune-related adverse effects caused by high doses. The advent of intratumoral immunotherapy has well addressed these issues. However, the efficacy of intratumoral immunotherapy alone is uncertain, as suggested by the results of preclinical and clinical studies. In this study, we will focus on the research of immunosuppressive tumor microenvironment with chemoablation and intratumoral immunotherapy, the synergistic effect between chemotherapeutic drugs and immunotherapy. We propose a new concept of intratumoral chemo-immunoablation. The concept opens a new perspective for tumor treatment from direct killing of tumor cells while, enhancing systemic anti-tumor immune response, and significantly reducing adverse effects of drugs.

Patients with triple‐negative breast cancer (TNBC) have the worst clinical outcomes when compared to other subtypes of breast cancer. Nanotechnology‐assisted photothermal therapy (PTT) opens new opportunities for precise cancer treatment. However, thermoresistance caused by PTT, as well as uncertainty in the physiological metabolism of existing phototherapeutic nanoformulations, severely limit their clinical applications. Herein, based on the clinically chemotherapeutic drug mitoxantrone (MTO), a multifunctional nanoplatform (MTO‐micelles) is developed to realize mutually synergistic mild‐photothermal chemotherapy. MTO with excellent near‐infrared absorption (≈669 nm) can function not only as a chemotherapeutic agent but also as a photothermal transduction agent with elevated photothermal conversion efficacy (ƞ = 54.62%). MTO‐micelles can accumulate at the tumor site through the enhanced permeability and retention effect. Following local near‐infrared irradiation, mild hyperthermia (<50 °C) assists MTO in binding tumor cell DNA, resulting in chemotherapeutic sensitization. In addition, downregulation of heat shock protein 70 (HSP70) expression due to enhanced DNA damage can in turn weaken tumor thermoresistance, boosting the efficacy of mild PTT. Both in vitro and in vivo studies indicate that MTO‐micelles possess excellent synergetic tumor inhibition effects. Therefore, the mild‐photothermal chemotherapy strategy based on MTO‐micelles has a promising prospect in the clinical transformation of TNBC treatment. A multifunctional drug delivery system (MTO‐micelles) based on the chemotherapeutic drug mitoxantrone (MTO) and amphiphilic polymer DSPE‐PEG2000 is developed. MTO induced DNA damage amplify the effect of Mild‐photothermal Chemotherapy by downregulating HSP70 expression. This mild‐photothermal chemotherapeutic formulation provides a facile and effective way for the TNBC treatment.

Melanoma is rare but dangerous skin cancer, and it can spread rather quickly in the advanced stages of the tumor. Abundant evidence suggests the relationship between tumor development and progression and the immune system. A robust gene risk model could provide an accurate prediction of clinical outcomes. The present study aimed to explore a robust signature of immune-related gene pairs (IRGPs) for estimating overall survival (OS) in malignant melanoma. Clinical and genetic data of skin cutaneous melanoma (SKCM) patients from The Cancer Genome Atlas (TCGA) was performed as a training dataset to identify candidate IRGPs for the prognosis of melanoma. Two independent datasets from the Gene Expression Omnibus (GEO) database (GSE65904) and TCGA dataset (TCGA-UVM) were selected for external validation. Univariate and multivariate Cox regression analyses were then performed to explore the prognostic power of the IRGPs signature and other clinical factors. CIBERSORTx was applied to estimate the fractions of infiltrated immune cells in bulk tumor tissues. A signature consisted of 33 IRGPs was established which was significantly associated with patients' survival in the TCGA-SKCM dataset (P = 2.0×10-16, Hazard Ratio (HR) = 4.220 (2.909 to 6.122)). We found the IRGPs signature exhibited an independent prognostic factor in all the three independent cohorts in both the univariate and multivariate Cox analysis (P<0.01). The prognostic efficacy of the signature remained unaffected regardless of whether BRAF or NRAS was mutated. As expected, the results were verified in the GSE65904 dataset and the TCGA-UVM dataset. We found an apparent shorter OS in patients of the high-risk group in the GSE65904 dataset (P = 2.1×10-3; HR = 1.988 (1.309 to 3.020)). The trend in the results of the survival analysis in TCGA-UVM was as we expected, but the result was not statistically significant (P = 0.117, HR = 4.263 (1.407 to 12.91)). CD8 T cells, activated dendritic cells (DCs), regulatory T cells (Tregs), and activated CD4 memory T cells presented a significantly lower fraction in the high-risk group in the TCGA-SKCM dataset(P <0.01). The results of the present study support the IRGPs signature as a promising marker for prognosis prediction in melanoma.

[This corrects the article DOI: 10.3389/fimmu.2022.1064047.].

BackgroundRARRES1 is a tumor suppressor protein, and its expression is suppressed in various tumor cells. However, whether it participates in the immune response in kidney renal clear cell carcinoma (KIRC) is unknown, and the defined mechanism is not clear. Therefore, the mechanism of RARRES1 in KIRC is worthy of investigation.MethodsWe analysed the expression and function of RARRES1 with The Cancer Genome Atlas (TCGA) database. The Kaplan–Meier curve was adopted to estimate survival. RARRES1-correlated genes were obtained from the UALCAN database and subjected to Gene Ontology (GO) enrichment and protein–protein interaction (PPI) network analyses. The correlation analysis between tumor-infiltrating immune cells and selected genes were performed with TIMER database. We also investigated the possible function of RARRES1 in KIRC by coculturing Caki-1 cells with THP-1 cells. Immunofluorescence assay was performed to study the RARRES1 expression in difference grade KIRC tissues.ResultsThe expression of RARRES1 was negatively correlated with survival in KIRC patients. The GO biological process term most significantly enriched with the RARRES1-correlated genes was regulation of cell adhesion. ICAM1, which exhibited a relatively highest correlation with RARRES1, is positively correlated with the infiltration level of macrophages. RARRES1 could enhance the expression of ICAM1 in Caki-1 cells and then induce the activation of M1 THP-1 cells to decrease the viability and induce the apoptosis of Caki-1 cells.ConclusionRARRES1 plays an antitumor role by promoting ICAM1 expression and inducing the activation of M1 macrophages. We offer insights into the molecular mechanism of KIRC and reveal a potential therapeutic target.

Ovarian clear cell carcinoma has a high recurrence rate with poor prognosis and is generally not sensitive to conventional platinum-based chemotherapy. Its less frequent occurrence of mutations such as BRCA limited the targeted therapies. Immunotherapy is not currently recommended as a first-line agent for ovarian cancer, and most patients are not yet able to benefit from it. Cryoablation can be used to treat solid systemic tumors, including ovarian cancer metastases, and can produce a limited anti-tumor immune response. The anti-tumor effects of cryoablation combined with immunotherapy have not been adequately confirmed. This study reports a case of a patient with ovarian clear cell carcinoma who underwent conventional adjuvant chemotherapy after initially surgical resection of the tumor. Unfortunately, cancer recurred and metastasized to the abdominal wall. After a series of painful chemotherapy and a second surgery, the cancer was still not effectively controlled, and the patient developed extensive metastases in the lung. The patient’s PD-L1 expression level also did not support solo immunotherapy. We pioneered the use of cryoablation to first eradicate the most significant lesion in the upper lobe of the left lung and then combined it with the PD-L1 inhibitor pembrolizumab to treat the patient with immunotherapy, which resulted in the complete eradication of the other multiple metastases in the lung and saved the patient’s life. Although the precise mechanism of action has not yet been explored, we have reason to believe that the combination of cryoablation and immune checkpoint inhibitor has a powerful synergistic anti-tumor effect, which is yet to be confirmed by more basic research and clinical applications in the next step.

Although intratumoral chemoablation can obtain an impressive therapeutic effect, there is still incomplete ablation and tumor recurrence in some patients. This could be due to the short retention time of the drug in the tumor, the limited distribution of intratumoral drugs, and, beyond that, the immunotolerance caused by the tumor microenvironment (TME). There is still an urgent need to find an optimal drug sustained-release carrier and figure out the impact of regional injection to TME. In this study, we supposed to use polyethylene glycol (PEG) hydrogel as a drug carrier to improve the retention time of the drug to extend the exposure of tumor cells and investigate the feasibility of combination local Epirubicin injection with anti-PD-L1. The results revealed obvious tumor suppression based on the tumor volume and the inhibition time of tumor growth in the A549 lung cancer mouse model after local injection. Furthermore, the enhanced antitumor effects of the combination of systematic anti- programmed death ligand 1 (PD-L1) therapy with local chemoablation (EPI-GEL/PD-L1) for abscopal tumor reduction in the 4T1 breast model were also observed. Flow cytometry analysis of the tumor and blood samples showed significant variations in the proportions of PD-L1 and CD3 CD8 PD-1 cells before and after anti-PD-L1 therapy. On day 4 after local injection of the EPI gel, the expression of PD-L1 in abscopal tumors was upregulated, while the expression of PD-L1 in bilateral tumors in mice was significantly reduced after anti-PD-L1 treatment. The proportion of CD3 CD8 PD-1 cells in the tumor and circulating blood in the EPI-GEL/PD-L1 group was decreased compared with that in the EPI-GEL (single injection of epirubicin) group. The combination of local injection of the chemoablation agent with anti-PD-L1 monoclonal antibody (mAb) therapy may strengthen the antitumor activity, and the use of PEG hydrogel as the drug carrier can extend the retention time of the chemoablation agent around the tumor, maintaining a long-term tumor-killing activity.