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e21514 Background: Tumor infiltrating lymphocytes (TILs) in the tumor microenvironment generate anti-tumor immunity and are associated with response to immune checkpoint inhibitor (ICI) therapy of melanoma. However, likelihood of response to ICI therapy depends upon intensity of TILs, proportion of effector and regulatory T cells and age. Methods: In a research study approved by the Institutional Review Board of University of Connecticut, we retrospectively analyzed outcome of patients diagnosed with cutaneous melanoma between 2009 and 2019 and developed unresectable stage III or stage IV disease requiring ICI treatment. Patients were stratified by age (< 75 and > 75 years old) and TILs at the primary cutaneous melanoma site categorized as brisk (present throughout vertical phase), non-brisk (present in one of more foci of vertical phase) or absent. Patient’s age at the time of metastases, as well as 12-month and 24-month overall survival (OS) following ICI treatment was recorded. Results: A total of 93 patients were screened, and 68 were included for analysis of survival outcome. Patients had to receive at least one dose of ICI treatment at UConn Health and had available data on TILs of primary cutaneous melanoma. In patients over 75 years of age, those with brisk TILs had an increased 24-month survival compared to those with non-brisk or absent TILs (100% vs. 45%, p = 0.04). In patients < 75 years of age, the 24 month survival was similar in those with brisk and non-brisk or absent TILs (67% vs. 69%, p = .91). There was no significant difference in overall survival between patients < 75 or > 75 years with brisk TILs (67% vs. 100%, p = .19). Additionally, in patients with non-brisk or absent TILs, there was a not quite significant difference in survival between those > 75 vs < 75 years (45% vs. 69%, p = .09). Conclusions: Our findings suggest that intensity of TILs in primary cutaneous melanoma is predictive of outcome following ICI treatment of advanced melanoma in patients over 75 years of age. These findings support possible interaction between qualitative differences of TILs and patient age. Our findings may help identify older melanoma patients who may benefit from ICI treatment.

144 Background: Anti-PD-1 therapy has become an effective method of treating patients including elderly subjects diagnosed with un-resectable or metastatic melanoma. While effective, toxicity reports in elderly are conflicting. Some reports indicate no added autoimmunity with older melanoma patients, while we had previously reported our concerns of heightened autoimmune toxicity with anti-PD-1 treatment of melanoma in elderly subjects. This report includes updated results in 36 patients receiving anti-PD-1 treatment for melanoma with an increased proportion of older subjects from a single institute. Methods: Between 2014-2018, we performed retrospective review of charts of patients treated with anti-PD-1 agents for stage III and IV melanoma following IRB approval. Data for treatment outcomes and grade III and IV immune related adverse events were collected. Results: 36 patients were treated with either Pembrolizumab or Nivolumab that included stage IV melanoma (28 pts), un-resectable stage III (5 pts) and stage III melanoma in adjuvant setting (3 pts). 30 out of 36 patients were over 60 years of age (median age 77, range 62-90) and 6 patients were younger than 60 years (median age 48, range 24-56). 16 out of 30 patients over age of 60 years (53%) experienced grade III or IV toxicities following anti-PD-1 therapy compared to none (0%) in age below 60 years. Overall, 19 patients are alive either with disease or on treatment with stable, partial or complete responses. 17 patients have died, out of which 12 died of progressive disease, 2 elderly patients died suddenly and 3 elderly patients died of autoimmune toxicity (myasthenia gravis like syndrome, acute inflammatory demyelinating polyneuropathy, pneumonitis). Some unusual autoimmune toxicity seen in elderly subjects included diabetes mellitus, Behcet disease, acute inflammatory demyelinating polyneuropathy, retinitis, Bell's palsy and bullous pemphigoid). Conclusions: Our data continue to indicate that increased risk of severe autoimmune toxicity following anti-PD-1 treatment involved older patients over 60 years of age. This finding may highlight the increased susceptibility of autoimmunity with aging.

e14603 Background: Immune checkpoint inhibitor (ICI) treatment has become effective method of treating mm including in those over 65 years of age. Increasing number of advanced age mm patients (pts.) are eligible for ICI treatment but not much is known about its efficacy and safety in relation to senescent immune system. We are reporting our updated experience of ICI treatment of advanced age mm pts. from a single Institute. Methods: Between 2011 and 2016, 32 eligible pts. diagnosed with mm were treated at the University of Connecticut with ICI including anti CTLA-4 antibody Ipilimumab, anti PD-1 antibody Pembrolizumab or combination of Ipilimumab and Nivolumab at their FDA approved doses on a standard protocol. Pts. were monitored for immune related adverse events (irAE) that were graded and managed with standard immune suppressive regimens Results: 12 out of 32 mm pts. were over 70 years of age (median 82.5 years, range 73-88 years). Nine pts. were treatment naïve, two had previously failed Ipilimumab treatment and one anti-BRAF and anti- MEK targeted therapy. Clinical benefit occurred in 5 out of 12 pts. (Complete response (CR) 3, partial response 1 and stable disease 1). Nine out of 12 pts. developed irAE that included three grade II (fatigue, diarrhea, hypopituitarism each) and 6 grade IV events (skin rash-1, colitis-1, encephalopathy-1, myasthenia gravis-1, and pneumonitis in 2 pts. each respectively). Of note, an 87-year-old male developed polymyalgia rheumatica after second dose of anti PD-1 treatment that responded to steroids, but developed autoimmune diabetes mellitus and pneumonitis following third dose. Two pts. died from irAE that included an 87-year-old woman from treatment refractory myasthenia gravis and 77-year-old male who suffered sudden death during steroid treatment of pneumonitis. Six pts. died of progressive disease including sudden death in a 77-year old woman and a 87-year-old male following five and two anti PD-1 treatments respectively. One pt. died from pulmonary embolism and four pts. are alive, 2 in CR and two with disease. Conclusions: Our experience indicate advanced age mm pts. respond to ICI treatment but have heightened risk of developing serious irAEs.

e21005Background: Melanoma is an immunogenic tumor incidence of which is rising at a rapid rate in the aging population that harbors a weakened and dysregulated immune system. Success of immune che...

e21135 Background: To understand the dynamics of anti tumor immune responses (IR) in the setting of the ageing immune system, we examined immunologically relevant gene transcripts in formalin fixed paraffin embedded (FFPE) primary cutaneous melanoma (PCM) samples derived from five young (age or=70 years) patients by qRT-PCR. Methods: A total of 10 FFPE tumor blocks were collected between 2004-2007 of patients with PCM at the University of Connecticut Health Center. Total RNA was extracted from FFPE tissue sections and random primed cDNA was generated. Pre amplification using pooled Taqman assays and Universal PCR Master Mix (Applied Biosystems, USA) was performed for 14 cycles to ensure an adequate amount of starting material for qPCR. Using 15 ng total RNA, the quantification of human IR genes (IL-2, INFg, TNFa, TGFb1, IL-10, Foxp3, and IDO-1) and transcripts of succinate dehydrogenase (SDHA) (as endogenous control) was accomplished by qRT-PCR amplification of a cDNA using TaqMan Universal PCR Master Mix and TaqMan gene expressions assay probes. All reaction assays including that of SDHA were performed in triplicate on an ABI 7500 Fast system (Applied Biosystems). Cycle threshold (Ct) values for each mRNA were normalized to SDHA (DCT) and represented as RQ=2-DCT. The average RQ was calculated for all ten samples in both cohorts and Student’s T-test was performed to evaluate the statistical significance of the IR gene expression. Results: While no significant difference of expression of Th1 cytokines (IL-2, IFNg, TNFa) or Th2/3 cytokines (IL-10, TGFb) could be detected within the two groups, FOXp3 expression was significantly decreased in PCM in the elderly. Conclusions: Our results suggest ageing may be associated with less regulatory responses in situ in PCM and that more expanded analyses of the nature of the IR in PCM are likely to provide information with implications on prognosis and immune based treatment options for elderly PCM subjects.

e19028 Background: Cutaneous melanoma (CM) incidence is rapidly rising in the elderly population resulting in treatment challenges and increased economic burden. Although old age is a marker of poo...

Publisher Summary This chapter discusses the control of photosynthetic sucrose formation. In most species, starch and sucrose are the principal end products of photosynthesis. It is clear that the formation of both carbohydrates is highly regulated biochemically. The interdependence of chloroplast and cytosolic metabolism implies that coordination of the fluxes and conditions in these compartments is a precondition for rapid photosynthesis. This interaction is defined by the stoichiometry of carbon and phosphate flow during steady-state photosynthesis. Chloroplasts convert three CO2 and one Pi to one molecule of triose-P, and a continuation of photosynthesis depends on the triose-P being removed and more Pi becoming available. This is achieved by exporting triose-P from the chloroplast, in exchange for Pi. However, the rate of this exchange must be coordinated with the rate of CO2 fixation, because only one-sixth of the triose-P may be removed, representing the net gain of carbon in one turn of the Calvin cycle.