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Targeted therapy and immunotherapy in combination is considered the ideal strategy for treating metastatic cancer, as it can eliminate the primary tumors and induce host immunity to control distant metastases. Phototherapy, a promising targeted therapy, eradicates primary tumors using an appropriate dosage of focal light irradiation, while initiating antitumor immune responses through induced immunogenic tumor cell death. Recently, phototherapy has been employed to improve the efficacy of immunotherapies such as chimeric antigen receptor T-cell therapy and immune checkpoint inhibitors. Phototherapy and immunoadjuvant therapy have been used in combination clinically, wherein the induced immunogenic cell death and enhanced antigen presentation synergy, inducing a systemic antitumor immune response to control residual tumor cells at the treatment site and distant metastases. This review summarizes studies on photo-immunotherapy, the combination of phototherapy and immunotherapy, especially focusing on the development and progress of this unique combination from a benchtop project to a promising clinical therapy for metastatic cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Early-life adversity can have long-lasting effects on physiological, behavioural, cognitive, and somatic processes. Consequently, these effects may alter an organism's life-history strategy and reproductive tactics.In response to early-life immune activation, we quantified levels of the acute phase protein haptoglobin (Hp) during development in male zebra finches ( Taeniopygia guttata ). Then, we examined the long-term impacts of early-life immune activation on an important static sexual signal, song complexity, as well as effects of early-life immune activation on the relationship between song complexity and a dynamic sexual signal, beak colouration. Finally, we performed mate-choice trials to determine if male early-life experience impacted female preference.Challenge with keyhole limpet hemocyanin (KLH) resulted in increased song complexity compared to lipopolysaccharide (LPS) treatment or the control. Hp levels were inversely correlated with song complexity. Moreover, KLH-treatment resulted in negative associations between the two sexual signals (beak colouration and song complexity). Females demonstrated some preference for KLH-treated males over controls and for control males over LPS-treated males in mate choice trials.Developmental immune activation has variable effects on the expression of secondary sexual traits in adulthood, including enhancing the expression of some traits. Because developmental levels of Hp and adult song complexity were correlated, future studies should explore a potential role for exposure to inflammation during development on song learning.Early-life adversity may differentially impact static versus dynamic signals. The use of phenotypic correlations can be a powerful tool for examining the impact of early-life experience on the associations among different traits, including sexual signals.

Secondary sexual traits may convey information about individual condition. We assessed the capacity for immune challenge with lipopolysaccharide (LPS) or keyhole limpet hemocyanin (KLH) during the prenatal and early postnatal stages to impact beak color development and expression in captive zebra finches. In addition, we tested whether adult immune challenge impacted beak color, and if early-life experience was influential. Immune challenge with KLH early in life slowed development of red beak coloration, and males challenged with KLH as nestlings had reduced red coloration as adults. Following adult KLH challenge, males exhibited a decline in beak redness. Birds challenged with KLH during development produced more anti-KLH antibodies after adult challenge. There was a significant interaction between young treatment and anti-KLH antibody production; for males not challenged with KLH early in life, individuals that mounted a weaker antibody response lost more red coloration after challenge than males mounting a stronger antibody response. Based on models of avian vision, these differences in beak coloration should be detectable to the finches. In contrast to previous studies, we found no effect of early-life or adult challenge with LPS on any aspects of beak coloration. These results provide evidence that beak color reflects developmental and current conditions, and that the signal is linked to critical physiological processes.

Metastatic melanoma is a skin cancer with poor prognosis. In situ photoimmunotherapy (ISPI) is a promising modality for the treatment of metastatic melanoma that combines local, selective photothermal therapy with immunological stimulation. A preliminary clinical study was conducted to evaluate the safety and therapeutic effects of ISPI for late-stage melanoma patients using imiquimod as the immune modifier. Eleven patients received ISPI in one or multiple 6-week treatment cycles applied to a 200-cm2 treatment site, which usually contained multiple cutaneous metastases. ISPI consisted of three main components applied directly to the cutaneous metastases: 1) local application of topical imiquimod; 2) injection of indocyanine green (ICG); and 3) an 805 nm laser for local irradiation. All patients completed at least one cycle of treatment. The most common adverse effects were rash and pruritus at the treatment sites. No grade 4 toxicity was observed. Complete response was observed in six patients. All lesions in the treatment area of the patients responded to ISPI, eight of which achieved complete local response (CLR). CLR was observed in the non-treatment site (regional) lesions in four patients. Five patients were still alive at the time of last follow-up. The probability of 12-month overall survival was 70%. This study demonstrates that ISPI with imiquimod is safe and well tolerated. The patient response rate is promising. ISPI can be easily applied on an outpatient basis and can be combined with other modalities to improve the therapeutic response of metastatic melanoma.

Melanoma vaccines are the best near term hope for improving mortality in patients with advanced disease. Although these vaccines are being developed for treatment of patients with advanced disease, their relatively low toxicity make them attractive for adjuvant therapy in stage I patients at high risk for recurrence. Recent developments in melanoma vaccines are reviewed and their importance to dermatologists is emphasized.

Thoracic splenosis is a rare condition resulting from concomitant rupture of the spleen and left hemidiaphragm, with autotransplantation of splenic tissue into the left hemithorax. It is usually an incidental finding on chest plain film or computed tomogram and is rarely diagnosed without biopsy or operation. A history of old splenic trauma and findings of left-sided, pleural-based nodules should indicate the diagnosis, which can be confirmed with nuclear medicine studies.

Formalin-fixed, paraffin-embedded primary melanoma biopsies were evaluated for evidence of genomic loss on the short arm of chromosome 9 using microsatellite PCR assays for the D9S157, D9S161 and D9S171 loci. Paired normal and tumor DNA was extracted from the same block for comparison of microsatellite marker patterns. Some detectable abnormality was seen in at least one of these loci in 15 of 44 evaluable specimens (34%). Homozygous deletions were detectable at these loci in 8 of 44 informative specimens (18%) and hemizygous deletions were seen in 11 of 44 informative specimens (25%). Deletions at 9p were more likely to be found as primary tumor thickness increased (p < 0.05). This evidence supports the concept that 9p21 deletions are involved in primary sporadic melanomas, and that 9p deletions are not solely an in vitro phenomenon.

The effects of a single exposure to UVB radiation on skin antioxidant enzymes and superoxide-generating xanthine oxidase were examined in Skh:HR-1 hairless mice. Significant decreases in superoxide dismutase (SOD) and catalase (CAT) were observed by 12 h after UV irradiation and remained depressed for up to 72 h. No induction of xanthine dehydrogenase (XD) or xanthine oxidase (XO) occurred with UV treatment, although significant hyperplasia was evident. Ornithine decarboxylase was induced after UV irradiation as has been previously reported. These results demonstrate significant biochemical effects of a single dose of UVB on murine epidermis, especially in terms of antioxidant defenses.