Nature killer cell therapy has shown strong efficacy in the field of oncology in recent years and has been applied to patients with metastases with the aim of improving the prognosis of advanced gastric cancer. A 59-year-old male with gastric adenocarcinoma with pancreatic metastasis (T4N0M1) who underwent radical surgery for gastric cancer with tumor metastasis was treated with oxaliplatin and tegafur combined with cellular reinfusion in stages. Computed tomograpy scan and serum tumor markers were monitored continuously after the treatment course. After five courses of combined treatment, the patient was in disease control with no significant side effects. At the last follow-up, the alpha fetoprotein had returned to its normal value with a poor display of low-density shadows in the body of the pancreas. Pancreatic cancer is insidious in origin and has a high mortality rate. The report provides clinical evidence for cell therapy of pancreatic metastatic cancer with improved quality of life.

Despite the emergence of monoclonal antibodies, the prognosis of patients with multiple myeloma (MM) with extramedullary disease remains poor. The present report describes a rare case of daratumumab-refractory MM that was successfully treated with elotuzumab, pomalidomide and dexamethasone. A 66-year-old male patient diagnosed with MM was treated with bortezomib, lenalidomide and dexamethasone, followed by high-dose chemotherapy and autologous stem cell transplantation. Thereafter, the patient was treated with lenalidomide and dexamethasone as maintenance therapy. This was changed to daratumumab, bortezomib and dexamethasone when new paraskeletal lesions were identified, resulting in marked tumor shrinkage. After 15 months, an increase in serum monoclonal protein levels, development of a skeletal lesion in the right second rib and extramedullary disease of the right thoracic mediastinal lymph nodes were noted. Treatment with elotuzumab, pomalidomide and dexamethasone (EPd) resulted in expeditious symptomatic improvement and regression of the lesions. Notably, during daratumumab, bortezomib and dexamethasone treatment, lymphocyte counts gradually increased to a level at which elotuzumab was sufficiently effective. EPd might be a promising strategy for the treatment of patients with relapsed extramedullary MM while on daratumumab treatment.

In a male with severe proctitis, monkeypox virus DNA was detected in skin lesions, blood, the nasopharynx, and the rectum, underlying generalized viral spreading. Rectal involvement was still found when skin lesions disappeared. At this early stage, an increase of cytotoxic and activated T cells was observed, while a reduction in CD56dimCD57+ NK cells compared with recovery time point was observed.

The study of inborn errors of immunity (IEI) provides unique opportunities to elucidate the microbiome and pathogenic mechanisms related to severe viral infection. Several immunological and genetic anomalies may contribute to the susceptibility to develop Human Papillomavirus (HPV) pathogenesis. They include different acquired immunodeficiencies, EVER1-2 or CIB1 mutations underlying epidermodysplasia verruciformis (EV) syndrome and multiple IEI. Whereas EV syndrome patients are specifically unable to control infections with beta HPV, individuals with IEI show broader infectious and immune phenotypes. The WHIM (warts, hypogammaglobulinemia, infection, and myelokathexis) syndrome caused by gain-of-CXCR4-function mutation manifests by HPV-induced extensive cutaneous warts but also anogenital lesions that eventually progress to dysplasia. Here we report alterations of B and NK cells in a female patient suffering from cutaneous and mucosal HPV-induced lesions due to an as-yet unidentified genetic defect. Despite no detected mutations in CXCR4, B but not NK cells displayed a defective CXCR4-dependent chemotactic response toward CXCL12. In addition, NK cells showed an abnormal distribution with an expanded CD56bright cell subset and defective cytotoxicity of CD56dim cells. Our observations extend the clinical and immunological spectrum of IEI associated with selective susceptibility toward HPV pathogenesis, thus providing new insight on the immune control of HPV infection and potential host susceptibility factors.

Natural killer (NK) cells play a key role in the control of cancer development, progression and metastatic dissemination. However, tumor cells develop an array of strategies capable of impairing the activation and function of the immune system, including NK cells. In this context, a major event is represented by the establishment of an immunosuppressive tumor microenvironment (TME) composed of stromal cells, myeloid-derived suppressor cells, tumor-associated macrophages, regulatory T cells and cancer cells themselves. The different immunoregulatory cells infiltrating the TME, through the release of several immunosuppressive molecules or by cell-to-cell interactions, cause an impairment of the recruitment of NK cells and other lymphocytes with effector functions. The different mechanisms by which stromal and tumor cells impair NK cell function have been particularly explored in adult solid tumors and, in less depth, investigated and discussed in a pediatric setting. In this review, we will compare pediatric and adult solid malignancies concerning the respective mechanisms of NK cell inhibition, highlighting novel key data in neuroblastoma and Wilms\' tumor, two of the most frequent pediatric extracranial solid tumors. Indeed, both tumors are characterized by the presence of stromal cells acting through the release of immunosuppressive molecules. In addition, specific tumor cell subsets inhibit NK cell cytotoxic function by cell-to-cell contact mechanisms likely controlled by the transcriptional coactivator TAZ. These findings could lead to a more performant diagnostic approach and to the development of novel immunotherapeutic strategies targeting the identified cellular and molecular targets.

OBJECTIVE: Natural killer (NK) cell enteropathy is a recently described clinically indolent condition characterised by atypical NK cell infiltrates in the gastrointestinal mucosa that mimics malignant lymphoma. We report a case that highlights the indolent clinical behaviour by documenting absence of clinical progression over 10 years.
RESULTS: We report the case of a 69-year old female who had clinically long-standing abdominal pain and recurrent mucosal ulcerations associated with atypical NK cell infiltrates. The clinical, morphologic and immunophenotypical findings in this case were diagnostic of NK cell enteropathy. Review of the patient\'s prior biopsies demonstrated that this persisted without clinical progression for 10 years, confirming the clinical indolent course.
CONCLUSIONS: Recognition of NK cell enteropathy is important to avoid over-diagnosing this benign condition as an aggressive lymphoma.

Natural killer (NK) cells are characterized by their ability to detect and induce apoptosis of susceptible target cells and by secretion of immunoregulatory cytokines such as IFN-γ. Activation of these effector functions is triggered upon recognition of tumor and pathogen (mostly virus)-infected cells and because of a bidirectional cross talk that NK cells establish with other cells of myeloid origin such as dendritic cells (DC) and macrophages. A common characteristic of these myeloid cells is their ability to secrete different members of the IL-12 family of cytokines such as IL-12, IL-23, and IL-27 and cytokines such as IL-15 and IL-18. Although the effect of IL-12, IL-15, and IL-18 has been characterized, the effect of IL-23 and IL-27 on NK cells (especially human) remains ill-defined. Particularly, IL-27 is a cytokine with dual functions as it has been described as pro- and as anti-inflammatory in different experimental settings. Recent evidence indicates that this cytokine indeed promotes human NK cell activation, IFN-γ secretion, NKp46-dependent NK cell-mediated cytotoxicity, and antibody (Ab)-dependent NK cell-mediated cytotoxicity (ADCC) against monoclonal Ab-coated tumor cells. Remarkably, IL-27 also primes NK cells for IL-18 responsiveness, enhancing these functional responses. Consequently, IL-27 acts as a pro-inflammatory cytokine that, in concert with other DC-derived cytokines, hierarchically contributes to NK cells activation and effector functions, which likely contributes to foster the adaptive immune response in different physiopathological conditions.