Dendritic cells loaded with killed breast cancer cells induce differentiation of tumor-specific cytotoxic T lymphocytes

BACKGROUND: Early clinical trials, mostly in the setting of melanoma, have shown that dendritic cells (DCs) expressing tumor antigens induce some immune responses and some clinical responses. A major difficulty is the extension to other tumors, such as breast carcinoma, for which few defined tumor-associated antigens are available. We have demonstrated, using both prostate carcinoma and melanoma as model systems, that DCs loaded with killed allogeneic tumor cell lines can induce CD8(+ )T cells to differentiate into cytotoxic T lymphocytes (CTLs) specific for shared tumor antigens. METHODS: The present study was designed to determine whether DCs would capture killed breast cancer cells and present their antigens to autologous CD4(+ )and CD8(+ )T cells. RESULTS: We show that killed breast cancer cells are captured by immature DCs that, after induced maturation, can efficiently present MHC class I and class II peptides to CD8(+ )and CD4(+ )T lymphocytes. The elicited CTLs are able to kill the target cells without a need for pretreatment with interferon gamma. CTLs can be obtained by culturing the DCs loaded with killed breast cancer cells with unseparated peripheral blood lymphocytes, indicating that the DCs can overcome any potential inhibitory effects of breast cancer cells. CONCLUSION: Loading DCs with killed breast cancer cells may be considered a novel approach to breast cancer immunotherapy and to identification of shared breast cancer antigens

Induction Chemotherapy in Head and Neck Squamous Cell Carcinoma: A Question of Belief

Induction chemotherapy (IC) in locally advanced head and neck squamous cell carcinoma (LA HNSCC) has been used for decades. However, its role is yet to be clearly defined outside of larynx preservation. Patients with high risk of distant failure might potentially benefit from sequential treatment. It is now widely accepted that TPF (docetaxel, cisplatin, and fluorouracil) is the standard IC regimen. Essays that have compared this approach with the standard of care, concurrent chemoradiotherapy (CCRT), are mostly inconclusive. Radiotherapy (RT) can be used in the post-IC setting and be sensitized by chemotherapy or cetuximab. Again, no consensus exists but there seems to be trend in favor of potentiation by cisplatin. Less toxic schemes of IC are tested as toxicity is a major issue with TPF. IC might have an interesting role in human papilloma virus (HPV)-related LA HNSCC and lead to CCRT de-escalation

Real World Data of Diagnosis, Survival, and Treatment Outcomes in Patients With Metastatic Non Clear Cell Renal Cell Carcinoma

Introduction: Metastatic non clear cell renal cell carcinoma (nccRCC) is an heterogenous group, usually excluded from phase 3 trials. We report real life data of prognosis and systemic management of those patients.Methods: We retrospectively included 102 metastatic nccRCC patients (unspecified papillary, n=10; type 1 and 2 papillary n=10 and n=32; translocation RCC, n=9; chromophobe, n=14; collecting duct, n=14) treated between 2006 and 2020.Objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were evaluated. Results: Among patients who underwent pathological review, 40.8% presented a complete histological discordance. First line treatments were mainly tyrosine kinase inhibitor (60.8%), combination including immunotherapy (7.8%) or combination of chemotherapy (13.7%). Median ORR ranged from 0% in unspecified papillary RCC to 42.9% in type 1 papillary RCC. Median PFS ranged from 2.9 months in collecting duct carcinoma to 10.9 months in type 1 papillary RCC. Median OS ranged from 6.8 months in collecting duct carcinoma to 29.1 months in MiT family translocation RCC. Thirty (29.4%) patients were included in a treatment trial during their treatment course.Conclusion: Metastatic nccRCC patients have variable prognosis due to heterogeneity of histological subtypes. Their diagnosis and access to therapeutic innovation remain suboptimal. Dedicated prospective trials are needed

Head and neck cancer and immunotherapy: current knowledge and perspective

As with many types of cancer, immunotherapy is changing the management of squamous cell carcinoma of the head and neck (HNSCC). In a locally advanced or metastatic setting, treatment options have long been curtailed, but this paradigm is currently changing. Checkpoint inhibitors were the first to be validated in second-line treatment with PD-1 and PD-L1 inhibitors and these treatments are available in USA for first-line use. In addition, many studies are underway to use its molecules earlier in the care or try to increase their effectiveness with associations. The issues of patient selection that would benefit the most from immunotherapy and the evaluation of the response to these treatments are not completely solved. The goal is here to update the possibilities of current treatment by immunotherapy in HNSCC as well as on various development pathways in progress

Cabazitaxel in recurrent/metastatic squamous cell carcinoma of the head and neck: Phase II UNICANCER trial ORL03

International audienceTreatments are limited after platinum Cetuximab or anti-PD1 failure for patients with recurrent/metastatic head and neck squamous cell carcinoma. Cabazitaxel has increased overall survival in hormone-refractory metastatic prostate cancer after failure of Docetaxel. Our aim was to detect a signal of activity with Cabazitaxel in patients with head and neck cancer who had failed platinum-, Cetuximab- and taxanes-based chemotherapy. This multicenter phase II trial included progressive patients with an ECOG ≤2. Cabazitaxel was given at 25 mg/m2/3 weeks (maximum of 10 cycles), with growth factors support. Efficacy was centralized and assessed every 6 weeks. The primary endpoint was control rate at six-weeks. A Simon's two-stage optimal design (P0=0.10; P1=0.30) required 29 evaluable patients. At the end of trial, at least 6 nonprogressions were required to consider the drug worthy of further study. Out of the 31 enrolled patients, 29 were eligible; 42% had received at least three previous lines of chemotherapy. For the primary end point, 8 patients (27.6%; 95%CI 12.7%-47.2%) had a stable disease at six weeks. Median progression-free survival was 1.05 months (95%CI 0.69-2.07). All patients were analyzed for toxicity: 6 patients had febrile neutropenia. During the 81 cycles administered, 49 grade 3-5 events were observed concerning 81% of the patients, including 35 severe adverse events of which 15 were related to Cabazitaxel. Although Cabazitaxel met its primary endpoint to deserve further investigations, its toxicity makes it difficult to use in frail patients and new schemes are needed (20 mg/m2 for example) if further investigations are launched

Radioresistance and genomic alterations in head and neck squamous cell cancer: Sub‐analysis of the ProfiLER protocol

International audienceBackgroundGenome analysis could provide tools to assess predictive molecular biomarkers of radioresistance.MethodsHead and neck squamous cell carcinoma patients included in ProfiLER study and who underwent a curative radiotherapy were screened. Univariate and Cox multivariate analyses were performed to explore the relationships between molecular abnormalities, infield relapse and complete tumor response after radiation.ResultsOne hundred and forty-three patients were analyzed. PIK3CA mutation and genomic instability of MAP kinases pathway were found to be prognostic factors of loco-regional relapse in multivariate analysis with respectively HR 0.33, 95% CI 0.13–0.83, p = 0.005 and HR 0.61, 95% CI 0.38–0.96, p = 0.025. Instability of apoptosis pathway was found to be a prognostic factor of complete response after radiotherapy with HR 0.24, 95% CI 0.07–0.88, p = 0.04.ConclusionThis sub analysis suggests that PIK3CA mutation, variation of copy number of MAP kinases and apoptosis pathways play a significant role in the radioresistance phenomeno