PD-1 monoclonal antibodies enhance the cryoablation-induced antitumor immune response: a breast cancer murine model research.

BACKGROUND: It has been demonstrated that cryoablation (Cryo) causes specific T-cell immune responses in the body; however, it is not sufficient to prevent tumor recurrence and metastasis. In this report, we evaluated changes in the tumor immune microenvironment (TIME) in distant tumor tissues after Cryo and investigated the immunosuppressive mechanisms that limit the efficacy of Cryo. METHODS: Bilateral mammary tumor models were established in mice, and we first observed the dynamic changes in immune cells and cytokines at different time points after Cryo. Then, we confirmed that the upregulation of PD-1 and PD-L1 signaling in the contralateral tumor tissue was closely related to the immunosuppressive state in the TIME at the later stage after Cryo. Finally, we also evaluated the synergistic antitumor effects of Cryo combined with PD-1 monoclonal antibody (mAb) in the treatment of breast cancer (BC) mouse. RESULTS: We found that Cryo can stimulate the body's immune response, but it also induces immunosuppression. The elevated PD-1/PD-L1 expression in distant tumor tissues at the later stage after Cryo was closely related to the immunosuppressive state in the TIME but also created the conditions for Cryo combined with PD-1 mAb for BC mouse treatment. Cryo + PD-1 mAb could improve the immunosuppressive state of tumors and enhance the Cryo-induced immune response, thus exerting a synergistic antitumor effect. CONCLUSIONS: The PD-1/PD-L1 axis plays an important role in suppressing Cryo-induced antitumor immune responses. This study provides a theoretical basis for Cryo combined with PD-1 mAb therapy in clinical BC patients.

Totally implantable venous access devices: The supraclavicular percutaneous approach and early complications.

BACKGROUND: The background of this study was to explore the success rate and early complications concerning the implantation of totally implantable venous access devices (TIVADs) by percutaneous venipuncture and management strategies for early complications. MATERIALS AND METHODS: This was a retrospective study of 1923 patients who received TIVAD implantation by percutaneous venipuncture (mostly via the supraclavicular route). The percutaneous access sites were internal jugular vein (810 patients; right/left: 158/652) or proximal right internal jugular vein, brachiocephalic vein, and proximal subclavian vein (1113 patients). Success rates and early complications related to TIVAD placement techniques were summarized, and strategies for managing complications were also analyzed. RESULTS: In 627 patients, TIVAD implantation was first performed by interventional radiologists using a "blind" approach relying on anatomical landmarks, having a 91.9% success rate. In contrast, there was a 100% success rate among the remaining 1296 patients who received ultrasound-guided implantation, a difference which was statistically significant (P < 0.05). Ultrasound-guided implantation was also successful for the 51 patients for whom the first attempt failed using the blind technique. Further, we found that the incidence of early complications was 5.41% (104/1923) and that the occurrence of immediate complications was significantly higher in the blind technique group compared to the ultrasound-guided group (37 vs. 12; P < 0.05). CONCLUSIONS: It is safe and feasible to implant TIVADs by supraclavicular venipuncture. Ultrasound guidance combined with X-ray monitoring during operation significantly improves the surgery success rate and reduces the risk of early complications. Unclear anatomical landmarks and vascular variation are the main factors affecting success using a blind (nonguided) technique.

[Detecting minimal residual disease status in allogeneic hematopoietic stem cell transplantation of patients with high-risk acute leukemia].

OBJECTIVE: To explore the relationship between minimal residual disease (MRD) and the outcome of patients with high-risk acute leukemia (AL) undergoing allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: By 4/5-color multi-parameter flow cytometry (MFC, CD45/SSC gating) for detecting MRD at pre-(day-30) and post-transplant (day +30, +60, +100, 6 months, 9 months and 12 months), the investigators retrospectively analyzed the MRD levels and the prognosis of 90 high-risk patients. According to the MRD cutoff value of 0.1%, the low-level and high-level groups were defined. In the high-level group, the patients were divided into two sub groups according to the subsequent treatment (intervention therapy group and non-intervention therapy group). RESULTS: MRD pre-transplant had no predictive value for the clinical outcome. The patients with high levels of MRD post-transplant (+60 d and +100 d) showed higher relapse rates than those of the low-level group. In addition, regarding MRD +100 d post-transplant, differences were significant among 3 groups (high-level MRD and intervention therapy group, high-level MRD and non-intervention therapy group and low-level MRD group) including 1-year relapse-free survival (RFS) (100% vs 60.87% vs 91.30%, P < 0.05) and 3-year RFS (85.71% vs 44.72% vs 68.48%, P < 0.05). The median time from first high level MRD detected to clinical relapse was 2.5 (1 - 26) months. In the high level MRD group (+100 d post-transplant), 7 of 30 patients received intervention therapy without relapse. However another 23 patients had no intervention treatment and 11 of them relapsed latter (P < 0.05). CONCLUSION: The MFC-based quantification of MRD post-transplant reveals important prognostic information in patients with high-risk AL. MRD check point at day +100 (cutoff: 0.1%) may discriminate different risk populations. Those patients with MRD levels ≥ 0.1% should receive early intervention at an early stage and a low tumor burden so as to reduce the relapse rate and boost survival.

[Surgical treatment and pathological findings of hematological malignancies patients complicated with lung diseases.].

OBJECTIVE: To determine the pulmonary pathological changes in hematological malignancy patients with pulmonary complications. METHODS: 17 hematological malignancy patients underwent surgical treatment were evaluated retrospectively. The pathological changes of all the surgical specimens were examined postoperatively by standard hematoxylin and eosin (HE) staining. RESULTS: Pathological examination confirmed: aspergillus infection in 9 patients, sub-acute inflammation (fibrosis and hematoma formation) in 3, and each in 1 of pulmonary infarction with granulomatous tissue in the periphery; granulomatous inflammation with calcified tubercle; alveolar dilation and hemorrhage, interstitial fibrosis and focal vasculitis; intercostal neurilemmoma; and moderate-differentiated adenocarcinoma accompanied by intrapulmonary metastasis. And several operative complications (1 case of fungal implantation, 3 pleural effusion and adhesions and 2 pulmonary hematoma) were occurred. The coincidence rate of pre- and post-operative diagnosis was 9/14 (64.3%). After surgery, 8 patients were received hematopoietic stem cell transplantation (HSCT, allo-gene or autologous), with 7 succeeded. On effective secondary antifungal prophylaxis, 4 of 5 patients of aspergillosis succeeded in transplantation with free from mycotic relapse, one patient died from fungal relapse. CONCLUSION: Hematological malignancies with persistent and/or resistant pulmonary infection, hemoptysis, or unexplained lung diseases, should be treated in time by surgery operation to effectively eliminate residual disease and obtain a definitive diagnosis, so as to create a prerequisite condition for the following treatments. Moreover, the secondary antifungal prophylaxis can provide active roles for patients scheduled for chemotherapy and/or HSCT.