NK Cells in Immunotherapy: How Important Are They?

AbstractNK cells are able to perform multiple functions, ranging from immunosurveillance to elimination of mutated or damaged cells, through many different cytotoxic mechanisms. Their functions can be very useful for cancer immunotherapy. But to achieve the maximum support from these extraordinary cells it is necessary to know their effector mechanisms and the mechanisms that lead to their suppression. We have briefly summarized some interesting aspect of their role in immunosurveillance of cancer and metastases, the major mechanisms of cell cytotoxicity, in particular their role in antigen dependent cell cytotoxicity, and many promising strategies currently under study to improve the anticancer function of these cells.Finally, we have taken a closer look at cell therapy in this context, comparing CAR-NK cells and CAR-T cells showing the potential advantages of the former over the latter

Follow-up in Head and Neck Cancer: Do More Does It Mean Do Better? A Systematic Review and Our Proposal Based on Our Experience

As the patients population ages, cancer screening increases, and cancer treatments improve, millions more head and neck carcinoma (HNC) patients will be classified as cancer survivors in the future. Change in epidemiology with human papillomavirus related HNC leads to a number of young treated patients. After treatment for HNC intensive surveillance, including ear, nose and throat (ENT) endoscopy, imaging, and serology, confers a survival benefit that became less evident in unresectable recurrence. We performed a comprehensive revision of literature and analyzed the experience of our centre. We revised publications on this topic and added data derived from the interdisciplinary work of experts within medical oncology, ENT, and radiation oncology scientific societies. We retrospectively collected local and distant recurrence of chemoradiation treated patients at Santa Croce and Carle University Hospital. A HNC follow-up program is not already codified and worldwide accepted. There is a need of scheduled follow-up. We suggest adopting a standardized follow-up guideline, although a multidisciplinary approach is frequently requested to tailor surveillance program and treatment on each patient

Fibroblast growth factor receptors as targets for anticancer therapy in cholangiocarcinomas and urothelial carcinomas

Cholangiocarcinomas and urothelial carcinomas are lethal tumors worldwide and only a minority of patients are eligible for surgery at diagnosis. Moreover, patients are poorly responsive to current therapeutic strategies, including chemotherapy, radiotherapy, immunotherapy, and multimodality treatments. Recently, several advances have been made in precision medicine and these results are modifying the treatment paradigm for patients diagnosed with cholangiocarcinomas and urothelial carcinoma. These histotypes exhibit a high rate of multiple fibroblast growth factor receptor (FGFR) genetic alterations and numerous preclinical and clinical studies support FGFR as a highly attractive novel therapeutic target. Moreover, identifying specific genetic alterations may predict the tumor's response to conventional and novel FGFRtargeted drugs. Recent clinical studies showed promising data for FGFR-targeted therapy in reducing tumor volume and led to the United States Food and Drug Administration (FDA) approval of, e.g., pemigatinib, infigratinib, futibatinib, and erdafitinib. Moreover, FGFR inhibitors show promising results in the first-line setting of cholangiocarcinomas and urothelial carcinomas. Pemigatinib (FIGHT-302) and futibatinib (FOENIX-CAA3) are being evaluated in phase III trials that compare these agents to current first-line gemcitabine and cisplatin in FGFR2-rearranged cholangiocarcinoma. However, complexity in targeting the FGFR signaling pathway is observed. Herein, we describe the characteristics of the FDA-approved and other investigational FGFRtargeted therapeutics, evaluate the most recent preclinical and clinical studies focusing on targeting FGFR genomic alterations in the treatment of cholangiocarcinomas and urothelial cancer, and provide insight into factors involved in response and (acquired) resistance to FGFR inhibition

Induction chemotherapy with paclitaxel and cisplatin to concurrent radiotherapy and weekly paclitaxel in the treatment of loco-regionally advanced, stage IV (M0), head and neck squamous cell carcinoma. Mature results of a prospective study

<p>Abstract</p> <p>Background</p> <p>to evaluate activity and toxicity of a sequential treatment in advanced, non metastatic, mostly unresectable, head and neck squamous cell carcinoma.</p> <p>Methods</p> <p>Patients with loco-regionally advanced or unresectable, head and neck cancer, were prospectively treated with 3 courses of induction chemotherapy followed by concurrent chemoradiation. Induction chemotherapy consisted of paclitaxel 175 mg/m2 day 1 and cisplatin 75 mg/m2 day 2, given every 3 weeks, to a total of three courses. Curative radiotherapy started 4 weeks after the last cycle of chemotherapy with the goal of delivering a total dose ≥ 66 Gy. During RT weekly paclitaxel (40 mg/m2) was administered.</p> <p>Results</p> <p>The trial accrued 43 patients from January 1999 to December 2002. All patients received 3 courses of induction chemotherapy and the planned dose of radiotherapy. Thirty-eight patients were able to tolerate weekly paclitaxel during irradiation at least for 4 courses. After induction therapy there were 32 overall responses, 74.4% (23 partial and 9 complete); at completion of concomitant treatment overall responses were 42, 97.7% (20 partial and 22 complete). Median time to treatment failure was 20 months and the disease progression rate at 3 and 5 years was 33% and 23%, respectively. The median overall survival time was 24 months and 3 and 5 years overall survival rates were 37% and 26%, respectively. The major toxicity was mucositis.</p> <p>Conclusions</p> <p>This combined treatment was found to be feasible and active in advanced or unresectable, head and neck squamous cell carcinoma patients. Long-term results observed in this trial encourage to consider this approach in further investigation using newer radiation delivering technique and new molecularly agents.</p

Infections in lung cancer patients undergoing immunotherapy and targeted therapy: an overview on the current scenario

Patients with a diagnosis of lung cancer are often vulnerable to infection, and the risk is increased by tumor-associated immunosuppression and the effects of the treatments. Historically, links between the risk of infection and cytotoxic chemotherapy due to neutropenia and respiratory syndromes are well established. The advent of tyrosine kinase inhibitors (TKIs) and immune-checkpoint inhibitors (ICIs) targeting the programmed cell death-1 (PD-1)/programmed cell death- ligand 1 (PD-L1) axis and cytotoxic T-lymphocyte antigen-4 (CTLA-4) have changed the treatment paradigm for lung cancer patients. Our understanding of the risk of infections while administrating these drugs is evolving, as are the biological mechanisms that are responsible. In this overview, we focus on the risk of infection with the use of targeted therapies and ICIs, summarizing current evidence from preclinical and clinical studies and discussing their clinical implications

A Multidisciplinary Approach to Patients with Psoriasis and a History of Malignancies or On-Treatment for Solid Tumors: A Narrative Literature Review

Psoriasis is a chronic immune-mediated disease that is linked to an increased risk of cancer. Although numerous studies have explored whether neoplasms are concurrent conditions or are induced by psoriasis, a definitive definition remains elusive. In this study, we conducted a comprehensive narrative literature review to offer practical guidance to oncologists and dermatologists regarding the initiation and discontinuation of biologics for psoriasis. The findings indicate that a customized approach is recommended for each patient, and that a history of malignancies does not constitute an absolute contraindication for biologics. Growing evidence supports the treatment of selected patients, emphasizing a nuanced assessment of benefits and risks. There is a lack of data specifying a safe timeframe to initiate biologics following a neoplasm diagnosis due to influences from cancer-related and patient-specific characteristics impacting prognosis. Some patients may continue anti-psoriasis therapy during cancer treatments. Enhanced comprehension of the biological mechanisms in cancer progression and the immune microenvironment of psoriasis holds promise for refining therapeutic strategies. In conclusion, a personalized treatment approach necessitates collaboration between oncologists and dermatologists, considering factors such as cancer prognosis, psoriasis clinical manifestations, patient characteristics, and preferences when making treatment decisions

Long-Term Effects of Breast Cancer Therapy and Care: Calm after the Storm?

Breast cancer is still a lethal disease and the leading cause of death in women, undermining patients' survival and quality of life. Modern techniques of surgery and radiotherapy allow for the obtaining of good results in terms of survival, however they cause long-term side effects that persist over time, such as lymphedema and neuropathy. Similarly, the advent of new therapies such as endocrine therapy revolutionized breast cancer outcomes, but side effects are still present even in years of follow-up after cure. Besides the side effects of medical and surgical therapy, breast cancer is a real disruption in patients' lives considering quality of life-related aspects such as the distortion of body image, the psychological consequences of the diagnosis, and the impact on family dynamics. Therefore, the doctor-patient relationship is central to providing the best support both during treatment and afterwards. The aim of this review is to summarize the consequences of medical and surgical treatment on breast cancer patients and to emphasize the importance of early prevention of side effects to improve patients' quality of life

Long noncoding RNAs as regulators of cancer immunity

Long noncoding RNAs (lncRNAs) are increasingly known to be important in cancer as they directly interact with the cell cycle, proliferation pathways and microbiome balance. Moreover, lncRNAs regulate the immune system: they do not directly encode proteins of innate or adaptive immunity, but regulate immune cell differentiation and function, such as dendritic cell activity, T cell ratio and metabolism. The result of this complex interaction is that lncRNAs regulate cancer processes through a complex multimodal system involving immunity, metabolism and infection. The possible functions of lncRNAs and their roles in the regulation of cancer immunity will be reported and discussed in the present review. Recent studies showed their function as regulators in the tumour microenvironment (TME), epithelial–mesenchymal transition, microbiota, metabolism and immune cell differentiation. However, there is not much knowledge regarding their roles in cancer immunity regulation. Thus, the main aim of this review is to describe lncRNAs that have specifically been associated with immunity, the immune cycle and the TME