raptor, Rickettsia in S. endius, and Sodalis in S. Irpagratinib cameroni. Low frequency of horizontal transmissions occurred in the interspecific combinations, but none of them persisted in the recipient species beyond F4, at most. Our study is one of few to demonstrate symbionts' horizontal transmission between hosts within the same trophic level and guild and highlights the rarity of such events. To appraise the available evidence on advanced practice physiotherapy (APP) models of care (MoC) in specialized secondary care such as orthopaedic, rheumatology or neurosurgery outpatients' clinics for adults with spinal pain. Systematic review with meta-analysis. Electronic searches were conducted up to July 2020 in Medline, Embase, Cochrane CENTRAL and CINAHL. Studies on APP MoC in specialized secondary care for adults with spinal pain were included. Eighteen studies (n = 9405), including two randomized controlled trials and sixteen observational studies were included. One study was considered at high quality, fourteen studies were considered of moderate quality and three were considered of low quality. Pooled results for change in disability for patients with spinal pain reported no significant difference between APP and usual medical care (UMC). Mean wait time for initial consultation was lower with APP (1-9.4weeks) than with UMC MoC (23-65weeks). Following the implementation of APP MoC, wait time for a consultation with a medical specialist was reduced (6-16weeks). Physiotherapists in APP MoC managed independently 89.2% of the patients referred (n = 8393). Stakeholders and patients reported high satisfaction with APP care. APP MoC and UMC likely result in comparable pain, disability and quality of life improvement for adults with spinal pain. However, APP MoC have the potential to improve health care access by reducing wait time for consultation in specialized care and maintaining a high level of satisfaction among stakeholders and patients.APP MoC and UMC likely result in comparable pain, disability and quality of life improvement for adults with spinal pain. However, APP MoC have the potential to improve health care access by reducing wait time for consultation in specialized care and maintaining a high level of satisfaction among stakeholders and patients.Identification of neoepitopes as tumor-specific targets remains challenging, especially for cancers with low mutational burden, such as ovarian cancer. To identify mutated human leukocyte antigen (HLA) ligands as potential targets for immunotherapy in ovarian cancer, we combined mass spectrometry analysis of the major histocompatibility complex (MHC) class I peptidomes of ovarian cancer cells with parallel sequencing of whole exome and RNA in a patient with high-grade serous ovarian cancer. Four of six predicted mutated epitopes capable of binding to HLA-A*0201 induced peptide-specific T cell responses in blood from healthy donors. In contrast, all six peptides failed to induce autologous peptide-specific response by T cells in peripheral blood or tumor-infiltrating lymphocytes from ascites of the patient. Surprisingly, T cell responses against a low-affinity p53-mutant Y220C epitope were consistently detected in the patient with either unprimed or in vitro peptide-stimulated T cells even though the patient's primary tumor did not bear this mutation. Our results demonstrated that tumor heterogeneity and distinct immune microenvironments within a patient should be taken into consideration for identification of immunogenic neoantigens. T cell responses to a driver gene-derived p53 Y220C mutation in ovarian cancer warrant further study. Nivolumab, a programmed death 1 (PD-1) inhibitor, has recently demonstrated efficacy as second-line therapy for esophageal squamous cell carcinoma (ESCC) patients in a phase III trial. We report real-world clinical outcomes of nivolumab therapy for ESCC patients. ESCC patients refractory/intolerant to at least one line of chemotherapy and who received nivolumab as a subsequent line of therapy were included. The efficacy and safety of nivolumab and the predictive role of PD-L1 and CD8 expression were analyzed. Fifty-eight patients were analyzed for safety and survival outcomes, while 57 were analyzed for objective response rates (ORR) excluding one with no measurable lesions. Eleven patients achieved a partial response, leading to an ORR of 19.3%. The median response duration was 6.5months (range 4.1-22.4). The median progression-free survival (PFS) and overall survival were 2.1 (95% confidence interval [CI] 1.8-2.3) and 7.4 (95% CI 4.8-10.0) months, respectively. Among patients with adequate samples, 56.9% (29/51), 27.5% (14/51), and 17.6% (9/51) expressed a combined positive score (CPS) ≥ 1, ≥ 10, and ≥ 20, respectively, while 24.4% (11/45) and 57.5% (23/40) were positive for intratumoral and peritumoral CD8 + T cell infiltration, respectively. A significantly longer PFS was observed in patients with a CPS ≥ 20 (7.5 [95% CI 1.8-13.1] vs. 1.9 [1.4-2.3] months, P = 0.05), and a trend towards better survival was seen in those with CPS ≥ 10 or intratumoral CD8 + T cell infiltration. Nivolumab is a valuable option at subsequent treatment lines for patients with advanced ESCC.Nivolumab is a valuable option at subsequent treatment lines for patients with advanced ESCC.Although immunotherapy has achieved impressive durable clinical responses, many cancers respond only temporarily or not at all to immunotherapy. To find novel, targetable mechanisms of resistance to immunotherapy, patient-derived melanoma cell lines were transduced with 576 open reading frames, or exposed to arrayed libraries of 850 bioactive compounds, prior to co-culture with autologous tumor-infiltrating lymphocytes (TILs). The synergy between the targets and TILs to induce apoptosis, and the mechanisms of inhibiting resistance to TILs were interrogated. Gene expression analyses were performed on tumor samples from patients undergoing immunotherapy for metastatic melanoma. Finally, the effect of inhibiting the top targets on the efficacy of immunotherapy was investigated in multiple preclinical models. Aurora kinase was identified as a mediator of melanoma cell resistance to T-cell-mediated cytotoxicity in both complementary screens. Aurora kinase inhibitors were validated to synergize with T-cell-mediated cytotoxicity in vitro.