A monoclonal has been isolated that labels an intracellular antigen in dendritic cells and some B cells. The M342 hamster immunoglobulin was selected because it stained cells in the periarterial sheaths of spleen, the deep cortex of lymph node, and the thymic medulla--the same regions in which one finds interdigitating cells, the presumptive in situ counterparts of isolated lymphoid dendritic cells. M342 labeled an antigen within granules of isolated dendritic cells, but only in cells that had been cultured for a day and not in fresh isolates. This extends recent findings that most freshly isolated spleen dendritic cells are located in the periphery of the white pulp nodule and may serve as precursors for the periarterial pool of interdigitating cells, the site for M342 staining in situ. By electron microscopic immunolabeling, the M342 antigen was found exclusively in a type of multivesicular body. M342 staining was not found in mononuclear phagocytes from blood and peritoneal cavity. Peritoneal B cells expressed M342+ granules, and upon appropriate stimulation splenic B cells developed reactive granules as well. We conclude that M342 is a strong marker for interdigitating cells. Its existence reveals intracellular specializations in the vacuolar system of antigen-presenting cells including subsets of dendritic cells.

The field of cardio-oncology is challenged to address an ever greater spectrum of cardiotoxicity associated with combination chemotherapy, greater dose intensity, extremes of age, and enhanced patient survival which exposes more protracted risk of developing congestive heart failure (CHF). Recent reports of chemotherapy-induced hypertension as a common adverse effect of angiogenesis inhibitors and immunosuppressants clarify the need for routine blood pressure (BP) monitoring and guideline-based management of hypertension as an integral strategy to preserve LV function. Serial monitoring of radionuclide left ventricular ejection fraction (LVEF) in adults and echocardiography in children continues to provide outcome based, cost-effective prevention of CHF in high risk patients receiving chemotherapy. To optimize treatment and monitoring strategies to eliminate late-onset LV dysfunction and CHF, traditional and novel candidate methods for assessment of chemotherapy-induced LV dysfunction are reviewed. These include serial assessment of LV volume indices by gated SPECT ERNA and gated SPECT MPI, 3D echocardiography and contrast 2D echocardiography; longitudinal strain imaging, diastolic functional parameters, 123 I-MIBG, 111 In-Antimyosin antibody imaging, and 99m Tc-Annexin V apoptosis imaging, biomarkers including troponins and BNP; genetic markers, and both functional and tissue characterization techniques with T1 weighted and T2 weighted images with cardiac magnetic resonance imaging (CMR). In our quest to optimize strategies for long-term cancer survival and prevention of CHF for patients receiving chemotherapy, rigorous modality and guideline-specific clinical outcome trials are required. A new multi-modality monitoring approach is proposed, which integrates evidencebased strengths of CMR, echocardiography, ERNA, biomarkers, and BP management for surveillance and validation of cardiotoxicity and prevention of clinical heart failure in patients receiving a broad spectrum of cancer therapies.

The mucosa of the conjunctiva is an important site of entry for environmental Ags as well as Ags emanating from the eye itself. However, very little is known about T cell recognition of Ag introduced through this important mucosal site. We have characterized the in vivo process of CD4 T cell recognition of Ag delivered via the conjunctival mucosa. Application of soluble OVA to the conjunctiva of BALB/c mice induced potent T cell tolerance. APC-presenting OVA peptide in vivo was only found in the submandibular lymph node and not in other lymph nodes, spleen, or nasal-associated lymphoid tissue. Similarly, in TCR transgenic DO11.10 adoptive transfer mice, OVA-specific CD4+ T cell clonal expansion was only observed in the submandibular lymph node following conjunctival application of peptide. These experiments thus define a highly specific lymphatic drainage pathway from the conjunctiva. OVA-specific T cell clonal expansion peaked at day 3 following initiation of daily OVA administration and gradually declined during the 10-day treatment period, but remained elevated compared with nontreated adoptive transfer mice. During this period, the T cells expressed activation markers, and proliferated and secreted IL-2 in vitro in response to OVA stimulation. In contrast, these cells were unable to clonally expand in vivo, or proliferate in vitro following a subsequent OVA/CFA immunization. These results suggest that Ag applied to a mucosal site can be efficiently presented in a local draining lymph node, resulting in initial T cell priming and clonal expansion, followed by T cell anergy.

Background Exercise can ameliorate cancer- and treatment-related toxicities, but poor adherence to exercise regimens is a barrier. Exercise interventions using digital activity trackers (E-DATs) may improve exercise adherence, but data are limited for patients with cancer. We conducted a systematic review examining the feasibility of E-DATs in cancer survivors and effects on activity level, body composition, objective fitness outcomes, health-related quality of life (HRQoL), self-reported symptoms, and biomarkers. Methods We identified randomized controlled trials (RCTs) of E-DATs in adult cancer survivors published in English between January 1, 2008, and July 27, 2017. Two authors independently reviewed article titles (n=160), removed duplicates (n=50), and reviewed the remaining 110 articles for eligibility. Results A total of 12 RCTs met eligibility criteria, including 1,450 patients (mean age, 50–70 years) with the following cancers: breast (n=5), colon or breast (n=2), prostate (n=1), acute leukemia (n=1), or others (n=3). Duration of E-DATs ranged from 4 to 24 weeks, and the follow-up period ranged from 4 to 52 weeks, with retention rates of 54% to 95%. The technology component of E-DATs included pedometers (n=8); pedometers with smartphone application (n=1), Wii Fit (n=1), heart rate monitor (n=1); and a wireless sensor with accelerometer, gyroscope, and magnetometer (n=1). Adherence by at least one measure to E-DATs was >70% in 8 of 8 RCTs. Compared with controls, E-DATs significantly improved patients’ step count in 3 of 5 RCTs, activity level in 6 of 9 RCTs, and HRQoL in 7 of 9 RCTs (all P≤.05), with no significant changes in biomarkers (eg, interleukin 6, tumor necrosis factor α, C-reactive protein, c-peptide, lipid panel) in 3 RCTs. Duration of E-DAT was not significantly correlated with adherence or study retention. Conclusions This systematic review shows that E-DATs are feasible to implement in cancer survivors. Future research should examine the optimal type, dose, and schedule of E-DATs for cancer survivors.

With the increasing number of individuals living with a current or prior diagnosis of cancer, it is important for the cardiovascular specialist to recognize the various complications of cancer and its therapy on the cardiovascular system. This is true not only for established cancer therapies, such as anthracyclines, that have well established cardiovascular toxicities, but also for the new targeted therapies that can have "off target" effects in the heart and vessels. The purpose of this informational statement is to provide cardiologists, cardiac imaging specialists, cardio-oncologists, and oncologists an understanding of how multimodality imaging may be used in the diagnosis and management of the cardiovascular complications of cancer therapy. In addition, this document is meant to provide useful general information concerning the cardiovascular complications of cancer and cancer therapy as well as established recommendations for the monitoring of specific cardiotoxic therapies.

Dendritic cells, well-known for their potent antigen-presenting activity, are generally present at very low frequency in the spleens of naive mice. We examined the ability of mice to generate functional dendritic cells (DC) following exposure to the cytokines interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Tumours secreting these cytokines provided a continuous stimulus resulting in a greatly increased number and frequency of DC in the spleen. These cells were purified by conventional DC isolation techniques and were found to exhibit many of the characteristics of DC from unmanipulated mice, including high allo-stimulatory activity in mixed lymphocyte reactions and expression of many similar cell surface markers. Using ovalbumin-peptide specific class I- and class II-restricted hybridomas containing the lacZ reporter gene, we found that these cytokine-generated DC had a greatly increased efficacy in the uptake and processing of particulate antigen. These cells appear to have retained the ability to ingest antigen that is generally associated with immature DC, but also exhibit the peptide/major histocompatibility complex (MHC)-presenting capabilities of mature DC. Development of an assay to measure the activity of a single DC revealed that these dual activities were the properties of the majority of the cytokine-generated DC. These findings indicate that exposure in vivo to the cytokines IL-3 and GM-CSF can result in the generation of large numbers of DC with increased capability of stimulating T cells. Thus, these cells may be important in vivo in the process of cross-priming and the subsequent generation of tumour-reactive cytotoxic T lymphocytes (CTL).

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