Postoperative Immunotherapy Research Articles

LncRNA-targeting bio-scaffold mediates triple immune effects for postoperative colorectal cancer immunotherapy

Colorectal cancer (CRC) recurrence after surgical resection results in poor clinical outcomes. Long noncoding RNAs (lncRNAs) are emerging new targets for mediating tumorigenesis and immunosuppression within tumor microenvironment. We develop a bio-scaffold encapsulating lncRNA-targeting biomimetic nanosystems for mediating triple immune effects against postoperative CRC recurrence. Liposome (termed as “D”)-decorated CRC cells’ membrane (CM) envelops a plasmid encoding a short hair-pinned RNA (shRNA) against plasmacytoma variant translocation 1 (Pvt1), forming the shPvt1-CM-D nanosystem. This nanosystem and the chemodrug Oxaliplatin (Oxa) are embedded in a hyaluronic acid and alginate-based bio-scaffold for postoperative implantation. (1) ShPvt1-CM-D-mediated Pvt1 knockdown strengthens Oxa-induced immunogenic cell death (ICD). (2) Such tumor antigens released from enhanced ICD and the CM from shPvt1-CM-D act as dual vaccines of dendritic cells. (3) Pvt1 knockdown by shPvt1-CM-D within granulocytic myeloid-derived suppressor cells (G-MDSCs) ameliorates G-MDSC-mediated immunosuppression. The nanosystem-carrying bio-scaffold significantly suppresses perioperative CRC local recurrence by 97.8% with survival rate (SR) of 62.5%. The bio-scaffold generates robust immune memory responses for completely suppressing tumor ectopic rechallenging and metachronous metastasis (SR: 100%). Additionally, the bio-scaffold reduces synchronously distant metastasis by 70.8%. This work presents a potent nanotechnology-facilitated lncRNA-targeting immunotherapy for postoperative CRC treatments.

Drug-Eluting Bead Bronchial Arterial Chemoembolization With and Without Microwave Ablation for the Treatment of Advanced and Standard Treatment-Refractory/Ineligible Non-Small Cell Lung Cancer: A Comparative Study.

PurposeTo compare the outcomes of drug-eluting bead bronchial arterial chemoembolization (DEB-BACE) with and without microwave ablation (MWA) for the treatment of advanced and standard treatment-refractory/ineligible non-small cell lung cancer (ASTRI-NSCLC).Materials and MethodsA total of 77 ASTRI-NSCLC patients who received DEB-BACE combined with MWA (group A; n = 28) or DEB-BACE alone (group B; n = 49) were included. Clinical outcomes were compared between groups A and B. Kaplan–Meier methods were used to compare the median progression-free survival (PFS) or overall survival (OS) between the two groups. Univariate and multivariate Cox proportional hazards analyses were used to investigate the predictors of OS for ASTRI-NSCLC treated with DEB-BACE.ResultsNo severe adverse event was found in both groups. Pneumothorax was the predominant MWA-related complication in group A, with an incidence rate of 32.1% (9/28). Meanwhile, no significant difference was found in DEB-BACE-related complications between groups A and B. The overall disease control rate (DCR) was 61.0% (47/77), with a significantly higher DCR in group A (85.7% vs. 46.9%, P = 0.002). The median PFS in groups A and B was 7.0 and 4.0 months, respectively, with a significant difference (P = 0.037). The median OS in groups A and B was both 8.0 months, with no significant difference (P = 0.318). The 6-month PFS and OS rates in groups A and B were 75.0% and 78.6%, 22.4% and 59.2%, respectively, while the 12-month PFS and OS rates in groups A and B were 17.9% and 28.6%, 14.3% and 22.4%, respectively. Of these, a significantly higher 6-month PFS rate was found in group A (75.0% vs. 22.4%; P < 0.001). The cycles of DEB-BACE/bronchial artery infusion chemotherapy [hazard ratio (HR): 0.363; 95% confidence interval (CI): 0.202–0.655; P = 0.001] and postoperative immunotherapy (HR: 0.219; 95% CI: 0.085–0.561; P = 0.002) were identified as the predictors of OS in ASTRI-NSCLC treated with DEB-BACE.ConclusionMWA sequentially combined with DEB-BACE was superior to DEB-BACE alone in the local control of ASTRI-NSCLC. Although the combination therapy reveals a trend of prolonging the OS, long-term prognosis warrants an investigation with a longer follow-up.

Promising alternatives of CD47 monoclonal antibody: an injectable degradable hydrogel loaded with PQ912 for postoperative immunotherapy effectively blocks CD47-SIRPα signal.

Rationale: Many cancers have evolved different mechanisms to evade immune surveillance. Macrophages, the innate defense of the immune system, are limited in their phagocytosis by CD47 anti-phagocytic signaling expressed on the surface of tumor cells. Although the CD47 monoclonal antibody (aCD47) strategy has been extensively studied in clinical trials, the depletion of aCD47 by red blood cells (RBCs) and the resulting hematotoxicity have impeded their application in tumor treatment.Methods: Here, we reported an injectable hydrogel scaffold that allowed for local delivery of small-molecule inhibitor PQ912. The biodegradable hydrogel scaffold (PQ/PB-Gel) was formed by rapid cross-linking of tetra-armed PEG succinimidyl succinate (Tetra-PEG-SS) solution and alkalescent bovine serum albumin (BSA) solution through ammonolysis reaction.Results: PQ/PB-Gel had excellent effect on inhibiting local recurrence of two kinds of tumors. The hydrogel system inhibited the generation of “don't eat me” signals during the treatment cycle by inhibiting the expression of newly generated neoplastic CD47. Thus, it avoided adverse reactions such as erythrocytopenia after the use of aCD47 in terms of safety. After the “don't eat me” signal was blocked the clearance and recognition of cancer cells by macrophages and antigen-presenting cells were enhanced, sequentially systemic immune response was activated and further memory T lymphocyte (T cell) formation was induced.Conclusions: PQ/PB-Gel had a simple preparation and administration method, low production cost, excellent efficacy and low toxicity, so it had good practicability. This might provide a safe alternative strategy for aCD47 for inhibit local tumor recurrence and distal metastasis in postoperative immunotherapy.

Specific immunotherapy in the complex treatment of ovarian cancer

The article is devoted to the search for new solutions in the field of treatment of malignant ovarian tumors and, in particular, new approaches for overcoming immune resistance in a complex method of therapy. The experience of treating this pathology with an original method of postoperative immunotherapy using autologous immunomodulators, which, due to its simplicity and relatively low cost, should be widely used in gynecological oncology, is considered.

Leptomeningeal disease and brain control after postoperative stereotactic radiosurgery with or without immunotherapy for resected brain metastases

PurposeImmunotherapy has shown activity in patients with brain metastases (BM) and leptomeningeal disease (LMD). We have evaluated LMD and intraparenchymal control rates for patients with resected BM receiving postoperative stereotactic...

Sodium Alginate Hydrogel-Mediated Cancer Immunotherapy for Postoperative In Situ Recurrence and Metastasis.

With the development of technology, adjuvant immunotherapy has become a promising strategy for prevention of postoperative tumor regression and metastasis by stimulating the host immune response. However, the therapeutic effects are still unsatisfactory due to the lack of synergy between different methods. In this study, an efficient synergistic immunotherapy system based on injectable sodium alginate hydrogels was designed to inhibit in situ recurrence and metastasis at the same time. On the one hand, an injectable sodium alginate (SA) hydrogel microsystem loaded with toll-like receptor (TLR) agonists (CpG ODNs) was synthesized for inhibiting in situ recurrence, and then carcinoembryonic antigen (CEA) probe was also added to detect CEA based on fluorescence resonance energy transfer (FRET) technology to monitor the occurrence and development of tumor recurrence. On the other hand, an anti-programmed cell death 1 ligand 1 antibody (anti-PD-L1)-modified SA nanogel loaded with indocyanine green (ICG@SA-anti-PD-L1 nanogel) was prepared for diagnosing and inhibiting lung metastasis by assisting orthotopic tumor therapy. In vitro and in vivo results demonstrated that this SA micro/nanosystem could monitor and inhibit postoperative recurrence and metastasis. We hope that this micro/nano-synergistic system will become an effective strategy for postoperative adjuvant immunotherapy.

Comparative analysis of postoperative adjuvant therapy for head and neck mucosal melanoma in China

Background Head and neck mucosal melanoma is a rare malignant disease with no clear and effective treatment to control the prognosis of patients. Aim To analyze the effects of different postoperative adjuvant treatments on the survival and prognosis of patients. Material and methods A retrospective analysis of 163 patients which were divided into five groups: no adjuvant therapy, postoperative radiotherapy, postoperative chemotherapy, postoperative chemotherapy and radiotherapy, and postoperative immunotherapy. Kaplan–Meier method and Cox regression analysis were used to analyze the prognosis in the different groups. Results Postoperative radiotherapy had statistically significant effects on local recurrence, distant metastasis, overall survival, progression-free survival (PFS) and recurrence-free survival (RFS); Postoperative chemotherapy and postoperative chemotherapy/radiotherapy had effects on distant metastasis, overall survival, PFS and RFS. However, postoperative immunotherapy did not show any significant effects. For patients with limited lesions who underwent endoscopic surgery, receive postoperative radiotherapy and postoperative chemotherapy/radiotherapy seem to have better prognosis. Conclusions and significance For the head and neck mucosal melanoma, different types adjuvant therapy can prolong the survival of patients to varying degrees compared with no postoperative treatment, but immunotherapy as a single adjuvant therapy does not show any advantages. We recommended that patients should receive radiotherapy and/or chemotherapy after surgery.

Effect of Postoperative Specific Immunotherapy Combined with Nasal Irrigation on Chronic Rhinosinusitis with Allergic Rhinitis

Patients with chronic rhinosinusitis (CRS) and allergic rhinitis (AR) (CRSwAR) have a more severe condition with a higher rate of recurrence after endoscopic sinus surgery (ESS). This study aimed to explore the effect of specific subcutaneous immunotherapy (SCIT) and nasal irrigation on CRSwAR after ESS. Sixty-four patients who were diagnosed as CRSwAR and received ESS were enrolled and divided into groups A, B, and C to receive different postoperative treatment strategies (conventional medication, medication with nasal irrigation, and medication with nasal irrigation and SCIT), and their prognosis was evaluated by scoring, electron microscopy, and inflammatory factors. One year after ESS, the recurrence rate of group C was significantly reduced; and the scoring from baseline was significantly different among the three groups, which of group C were the best. The epithelium arrangement, cilia morphology, and inflammation of nasal mucosa in each group were better than those in the preoperative state; and those in group C were the best. After one year, the expression levels of eosinophil cationic protein (ECP), interleukin (IL)-8, and IL-17 in group B were lower than those of group A; and the expression levels of ECP, IL-8, IL-25, IL-33, IL-17 in group C were lower than those in group A. SCIT combined with nasal irrigation can improve the patients' symptoms and quality of life, promote the epithelialization of the mucosa in the surgical cavity, regulate the local immune response of the nasal cavity; thus improve the prognosis of patients with ESS after 1 year.

Immune landscape and subtypes in primary resectable oral squamous cell carcinoma: prognostic significance and predictive of therapeutic response

BackgroundImmune landscape of cancer has been increasingly recognized as a key feature affecting disease progression, prognosis and therapeutic response. Here, we sought to comprehensively characterize the patterns of tumor-infiltrating immune...

Biopolymer Immune Implants' Sequential Activation of Innate and Adaptive Immunity for Colorectal Cancer Postoperative Immunotherapy.

Surgical resection is the first-line therapy for colorectal cancer (CRC). However, for advanced CRC, the curative effect of surgical resection is limited due to either local recurrence or distal metastasis. Postoperative in situ immunotherapy, presents a promising option for preventing tumor recurrence and metastasis, owing to the fact that surgeons have unique opportunities and direct access to the surgical site. Herein, a designed biopolymer immune implant for CRC post-surgical therapy, characterized with tissue adhesion, sustained drug release, and sequential elicitation of innate immunity, adaptive immunity, and immune memory effects, is reported. With gradual release of the loaded resiquimod (R848) and anti-OX40 antibody (aOX40), the immune implant can eradicate residual tumors post-surgery (with no tumor recurrence in 150 days), inhibit the growth of distal tumors and elicit immune memory effects to resist tumor re-challenge. Immunological analysis reveal that the biopolymer immune plant treatment leads to a two-stage action, with enhanced natural killer cells (NK cells) infiltration and activation of dendritic cells (DCs) in the first several days, then a greatly increased population of infiltrating T cells, and finally immune memory effects are established. The reported biopolymer immune implants provide a valuable and clinically-relevant option for post-surgical CRC management.

Postoperative Therapy for Resected Squamous Cell Carcinoma of the Head and Neck (SCCHN): Initial Findings of an American Radium Society (TM) (ARS) Appropriate Use Criteria Systematic Review (SR)

Progress in SCCHN management requires re-evaluation of postoperative therapy for resected SCCHN. Since the ARS and American College of Radiology (ACR) published a literature review and expert consensus guideline on postoperative therapy in 2011, additional relevant clinical trials have been published. To comprehensively evaluate existing prospective clinical studies of postoperative therapy for resected SCCHN using a formalized methodologic approach described by the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) Protocol, and to identify areas of accepted recommendations, controversy and uncertainty. The methodologic protocol for this SR was guided by PRISMA. Ovid Medline and Embase were searched on 01/10/2019 using medical subject headings designed to capture all published studies of HN cancer and postoperative therapy. The PICO (participants, interventions, comparators, outcomes) framework was used to identify published randomized trials, single and multi-arm non-randomized prospective clinical trials, and SRs/meta-analyses that adhered to a published methodology. Longitudinal prospective cohort studies were included if there was a baseline pre-intervention assessment. Excluded studies had <20 patients, were in non-English languages, or were case reports, case series, retrospective studies, large database studies, abstracts, preliminary analyses, narrative reviews, modeling studies, cell-line or non-clinical/non-human studies. Articles were selected if the population included adult patients with stage I-IVB SCCHN and no prior HN radiation who were treated with curative-intent surgery. Included disease sites were: oral cavity, oropharynx, hypopharynx, and larynx. The interventions of interest were postoperative radiation therapy (PORT), chemo-PORT, or postoperative chemotherapy, biologic therapy, targeted therapy, and/or immunotherapy. Studies were selected using Covidence ® software by two independent reviewers based on study relevance related to the inclusion/exclusion criteria. Each study was graded using the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence Table. A total of 5,689 studies were identified. After removal of duplicates, 5,660 studies were screened using the title and abstract, leading to 201 studies assessed for relevance using full-text review. After limitation to the eligibility criteria, 96 studies were identified. An additional 4 eligible studies were added that were published after the cut-off date or were not identified through the literature search. Studies with primary oncologic endpoints included 11 SRs, 24 randomized trials, 28 non-randomized trials, and 9 post-hoc analyses of randomized trials. Studies of non-oncologic endpoints included 2 SRs, 1 randomized trial, and 21 non-randomized clinical trials. This comprehensive, rigorously conducted SR identified 96 published prospective studies of postoperative therapy for SCCHN that constitute the evidence base for the ARS AUC HN Committee’s systematic review. Recommendations and identification of areas of continuing disagreement requiring further research will be generated from this evidence base; these will be described in more detail at the time of presentation.

Endovascular treatment with in-vitro fenestration and sac filling technique for ruptured thoracoabdominal aortic aneurysm with Behcet\u2019s disease

PurposeWe provided an endovascular strategy of treating ruptured aortic aneurysm with Behcet’s Disease.Case reportA 25-year-old man was diagnosed ruptured thoracoabdominal aortic aneurysm with Behcet’s Disease according to his eye damage history, high level of ESR and C-reactive protein and the imaging result. We used in-vitro fenestration of the stent-graft combined with in-stent technique to occlude the ruptured aortic aneurysm and preserve the blood supply from the aorta for visceral arteries in emergency. Sac filling technique was used to treat the endoleak to quickly prevent bleeding. The patient kept post-operative immunotherapy for 1 year.ConclusionThe patient had a good prognosis in the reduction of the cavity of aortic aneurysm to the normal size without any complications in a year follow-up.

Immunotherapy in patients with local HPV infection and high-grade squamous intraepithelial lesion following uterine cervical conization

Objective To establish the clearance of cervical human papillomavirus (HPV) infection following postoperative immunotherapy with inosine pranobex in women receiving surgical treatment of established high-grade squamous intraepithelial lesion (HSIL) of the uterine cervix. Materials and methods Over the six-year study period, 32 women with cervical HPV infection following electroconization (loop electrosurgical excision procedure) of the uterine cervix for established HSIL were randomly divided into two groups: I (n = 10) without and II (n = 22) with postoperative inosine pranobex immunotherapy. Follow-up after 24 and 48 months included cervical testing for HPV persistence and after 12, 24, and 48 months with cytology and colposcopy for dysplasia relapse (confirmed histologically). Results Relapse monitoring in 32 women after 12 months revealed 1 and 0 HSIL positive in groups I and II, respectively; after 24 months an additional 3 patients in each group were positive; and after 48 months an additional 3 and 1 patients were positive in groups I and II, respectively (p < .05). The groups significantly differed (p < .05) with regard to clearing the most common high-risk HPV genotypes (HPV 16 and HPV 56). Conclusions Inosine pranobex immunotherapy in HPV-positive patients following cervical conization significantly increased the clearance of viral infection with high-risk genotypes and reduced relapse of HSIL.

CIK cell cytotoxicity is a predictive biomarker for CIK cell immunotherapy in postoperative patients with hepatocellular carcinoma.

Adjuvant cytokine-induced killer (CIK) cell immunotherapy has shown potential in improving the prognosis of hepatocellular carcinoma (HCC) patients after curative resection. However, whether an individual could obtain survival benefit from CIK cell treatment remains unknown. In the present study, we focused on the characteristics of CIK cells and aimed to identify the best predictive biomarker for adjuvant CIK cell treatment in patients with HCC after surgery. This study included 48 patients with HCC treated with postoperative adjuvant CIK cell immunotherapy. The phenotype activity and cytotoxic activity of CIK cells were determined by flow cytometry and xCELLigence™ Real-Time Cell Analysis (RTCA) system, respectively. Correlation analysis revealed that the cytotoxic activity of CIK cells was significantly negative correlated with the percentage of CD3+ CD4+ cell subsets, but significantly positive correlated with CD3-CD56+ and CD3+ CD56+ cell subsets. Survival analysis showed that there were no significant associations between patients' prognosis and the phenotype of CIK cells. By contrast, there was statistically significant improvement in recurrence-free survival (RFS) and overall survival (OS) for patients with high cytotoxic activity of CIK cells as compared with those with low cytotoxic activity of CIK cells. Univariate and multivariate analyses indicated that CIK cell cytotoxicity was an independent prognostic factor for RFS and OS. In conclusion, a high cytotoxic activity of CIK cells can serve as a valuable biomarker for adjuvant CIK cell immunotherapy of HCC patients after surgery.

Co-localized delivery of nanomedicine and nanovaccine augments the postoperative cancer immunotherapy by amplifying T-cell responses

Immunotherapy in solid tumors is limited by the poor immunogenicity of tumors and limited T-cell immune response, resulting in low patient response rate. To increase the efficiency of cancer immunotherapy, a unique synergistic combination cancer immunotherapy by co-localized delivery of cancer nanomedicine for enhancing the tumor immunogenicity and nanovaccine for augmenting the antitumor T-cell immunity was developed for post-surgical tumor treatment. The thermo-responsive, curcumin-loaded polymer nanoparticles (nanomedicine)-assembled hydrogel enabled the complete coverage of the surgical bed of primary tumor and the spatio-temporal delivery of cognate nanomedicines and encapsulated nanovaccines. Importantly, the nanomedicine efficiently induced the immunogenic cell death (ICD) of residual cancer cells, and consequently enhanced the tumor immunogenicity and sensitized the tumor to antitumor T-cell immunity. The cancer nanovaccine composed of antigenic peptide, CpG-ODN and cationic polymer nanoparticle significantly triggered the maturation of dendritic cells (DCs) and elicited potent vaccine-specific T-cell immune responses. Using highly malignant postoperative breast carcinoma 4T1 models, we found that the combination immunotherapy strategy strikingly amplified the level of systemic host T-cell immunity, promoted the infiltration of CD8+ T lymphocytes in tumor, and thus efficaciously attenuated the local tumor recurrence and pulmonary metastasis. Collectively, this work provided an advanced synergistic combination approach for post-surgical tumor immunotherapy. The self-assembled hydrogel should enable a broader combination of immunomodulating nanomedicines and vaccines for cancer immunotherapy.

Rapamycin Prevents Surgery-Induced Immune Dysfunction in Patients with Bladder Cancer.

The mechanistic target of rapamycin (mTOR) integrates environmental inputs to regulate cellular growth and metabolism in tumors. However, mTOR also regulates T-cell differentiation and activation, rendering applications of mTOR inhibitors toward treating cancer complex. Preclinical data support distinct biphasic effects of rapamycin, with higher doses directly suppressing tumor cell growth and lower doses enhancing T-cell immunity. To address the translational relevance of these findings, the effects of the mTOR complex 1 (mTORC1) inhibitor, rapamycin, on tumor and T cells were monitored in patients undergoing cystectomy for bladder cancer. MB49 syngeneic murine bladder cancer models were tested to gain mechanistic insights. Surgery-induced T-cell exhaustion in humans and mice and was associated with increased pulmonary metastasis and decreased PD-L1 antibody efficacy in mouse bladder cancer. At 3 mg orally daily, rapamycin concentrations were 2-fold higher in bladder tissues than in blood. Rapamycin significantly inhibited tumor mTORC1, shown by decreased rpS6 phosphorylation in treated versus control patients (P = 0.008). Rapamycin reduced surgery-induced T-cell exhaustion in patients, evidenced by a significant decrease in the prevalence of dysfunctional programmed death-1 (PD-1)-expressing T cells. Grade 3 to 4 adverse event rates were similar between groups, but rapamycin-treated patients had a higher rate of wound complications versus controls. In conclusion, surgery promoted bladder cancer metastasis and decreased the efficacy of postoperative bladder cancer immunotherapy. Low-dose (3 mg daily) oral rapamycin has favorable pharmacodynamic and immune modulating activity in surgical patients and has the potential to decrease surgery-induced immune dysfunction.

A cancer vaccine-mediated postoperative immunotherapy for recurrent and metastatic tumors

Vaccines to induce effective and sustained antitumor immunity have great potential for postoperative cancer therapy. However, a robust cancer vaccine simultaneously eliciting tumor-specific immunity and abolishing immune resistance continues to be a challenge. Here we present a personalized cancer vaccine (PVAX) for postsurgical immunotherapy. PVAX is developed by encapsulating JQ1 (a BRD4 inhibitor) and indocyanine green (ICG) co-loaded tumor cells with a hydrogel matrix. Activation of PVAX by 808 nm NIR laser irradiation significantly inhibits the tumor relapse by promoting the maturation of dendritic cells and eliciting tumor infiltration of cytotoxic T lymphocytes. A mechanical study reveals that NIR light-triggered antigen release and JQ1-mediated PD-L1 checkpoint blockade cumulatively contribute to the satisfied therapeutic effect. Furthermore, PVAX prepared from the autologous tumor cells induces patient-specific memory immune response to prevent tumor recurrence and metastasis. The PVAX model might provide novel insights for postoperative immunotherapy.

Implantable Synthetic Immune Niche for Spatiotemporal Modulation of Tumor-Derived Immunosuppression and Systemic Antitumor Immunity: Postoperative Immunotherapy.

The development of biomaterial-based immune niches that can modulate immunosuppressive factors in tumor microenvironment (TME) will be a key technology for improving current cancer immunotherapy. Here, implantable, engineered 3D porous scaffolds are designed to generate synergistic action between myeloid-derived suppressor cell (MDSC)-depleting agents, which can accommodate the establishment of a permissive immunogenic microenvironment to counteract tumor-induced immunosuppression, and cancer vaccines consisting of whole tumor lysates and nanogel-based adjuvants, which can generate tumor antigen-specific T cell responses. The local peritumoral implantation of the synthetic immune niche (termed immuneCare-DISC, iCD) as a postsurgical treatment in an advanced-stage primary 4T1 breast tumor model generates systemic antitumor immunity and prevents tumor recurrence at the surgical site as well as the migration of residual tumor cells into the lungs, resulting in 100% survival. These therapeutic outcomes are achieved through the inhibition of immunosuppressive MDSCs in tumors and spleens by releasing gemcitabine and recruitment/activation of dendritic cells, enhanced population of CD4+ and CD8+ T cells, and increased IFN-γ production by cancer vaccines from the iCD. This combined spatiotemporal modulation of tumor-derived immunosuppression and vaccine-induced immune stimulation through the iCD is expected to provide an immune niche for prevention of postoperative tumor recurrence and metastasis.

Primary High-Grade Non-Muscle-Invasive Bladder Cancer: High NFκB Expression in Tumor Specimens Distinguishes Patients Who are at Risk for Disease Progression.

To investigate the potential prognostic role of NFκB expression in primary high-grade non-muscle-invasive bladder cancer. Patients with primary high-grade non-muscle-invasive bladder cancer who received induction and maintenance BCG therapy were retrospectively included. Recurrence and progression were histologically proven. Intensity and extent of immunochemistry were assessed. The final evaluation of the NFκB staining was done by combining intensity and extent as ΄΄product΄΄ and expressing it as ΄΄low NFκΒ expression΄΄ or ΄΄high NFκB expression΄΄. Epidemiological, pathological, clinical parameters and NFκB expression were statistically analyzed for recurrence (REC), progression (PR), recurrence-free survival (RFS) and progression-free survival (PFS). NFκB is significantly associated with disease progression (p<0,001 in univariate analysis and p=0,001, Odds Ratio=14,484, 95% Confidence Interval=3187-65,821 in multivariate analysis), but not with recurrence. The median value of NFκB expression as ΄΄product΄΄ is significantly higher for the patients with progression in comparison to patients with recurrence only (p=0,003) and patients without recurrence or progression (p=0,001). Patients' age is significantly associated (p=0,001 in univariate analysis and p=0,003, Odds Ratio=1273, 95% Confidence Interval=1086-1492 in multivariate analysis) with disease recurrence. High NFκB expression in primary high-grade non-muscle-invasive bladder cancer, treated with postoperative intravesical BCG immunotherapy, could represent an unfavorable prognostic factor.

Effects of Autologous Cytokine-Induced Killer Cells Infusion in Colorectal Cancer Patients: A Prospective Study.

To evaluate the efficacy and safety of postoperative adjuvant immunotherapy with cytokine-induced killer (CIK) cells in combination with chemotherapy (CT) in colorectal cancer (CRC) patients. A total of 46 patients were randomly assigned to either group 1 (control group) or group 2 (CIK group) using blocked randomization. Both groups received the FOLFOX4 (5-fluorouridine, leucovorin, and oxaliplatin) CT. In the CIK group, patients were given CIK cell infusion after FOLFOX4 CT. Treatment efficacy, adverse effects, and quality of life (QOL) were assessed. During the first 2 years of follow-up, the recurrence rate in the CIK group (26.1%, 6 in 23 cases) was significantly lower than the control group (43.5%, 10 in 23). The survival time was significantly longer in the CIK group (41.9 months, 95% confidence interval [CI]: 38.2-45.7) than in the control group (33.8 months, 95% CI: 28.4-39.2). Although QOL was reduced in both treatment groups, adjuvant CIK cell transfusion significantly improved the QOL in patients with CRC. Toxicity was mild in patients with CIK treatment. Immunotherapy with CIK cells may serve as an adjuvant treatment in patients with CRC after CT with prolonged survival of patients, limited side-effects, and improved QOL.