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While immunotherapy has revolutionized the treatment of many types of advanced cancer, most patients still do not derive benefit. The currently available immune checkpoint inhibitors target the adaptive immune system, generating a T-cell antitumor response. However, an antitumor immune response depends on a complex interplay of both innate and adaptive immune cells. The innate immune system is a promising new target, and innate immune checkpoint inhibitors can disrupt inhibitory interactions (“don't eat me” signals) between tumor and both phagocytes and natural killer cells. The checkpoint inhibitor may also provide a stimulatory interaction (“eat me” signal), or this can be achieved through use of combination therapy. This generates antitumor effector functions including phagocytosis, natural cytotoxicity, antibody-dependent effects, and synergistic activation of the adaptive immune system via antigen presentation. This is a rapidly expanding area of drug development, either alone or in combination (with anticancer antibodies or adaptive immune checkpoint inhibitors). Here, we comprehensively review the mechanism of action and up-to-date solid tumor clinical trial data of the drugs targeting phagocytosis checkpoints (SIRPα/CD47, LILRB1/MHC-I, and LILRB2/MHC-I) and natural killer–cell checkpoints (TIGIT/CD112 + CD155, PVRIG/CD112, KIRs/MHC-I, and NKG2A-CD94/HLA-E). Innate immune checkpoint inhibitors could once again revolutionize immune-based cancer therapies.

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment of relapsed/refractory (R/R) B-cell lymphomas, though certain patients do not respond to treatment or relapse afterwards. The purpose of this study is to determine patient variables that are predictive of response to CAR-T therapy.We conducted a retrospective review of 59 R/R B-cell non-Hodgkin lymphoma patients who received anti-CD19 CAR T-cell therapy. Risk factors for progression free survival (PFS) and overall survival (OS) were identified and multivariate logistic regression models for PFS and OS at 1 year were created using stepwise selection. The final multivariate logistic regression models were used to estimate the area under the receiver operating curve (AUROC).At median follow up of 25.6 months, median overall survival was not reached, and median progression free survival was 5.7 months. Stage IV disease (odds ratio (OR) 9.335, P = .025) was identified as a predictive variable for progression at day 365 with an AUC of 0.7922 (P.001). IPI (OR 2.828, P = .014), ALC ≥ 0.50 at collection (OR 0.183, P = .043), CRP ≥ 11 (OR 6.177, P = .019), and tocilizumab administration (OR 0.062, P = .005) as predictors for death at day 365 with an AUC 0.8626 (P.001).Clinical variables identify R/R lymphoma patients who are at risk for progression and poor overall survival after CAR T-cell therapy. IPI, CRP, ALC, and tocilizumab administration may be predictors of survival.

10604 Background: Individuals with hereditary cancer syndromes (HCS) have a high lifetime risk of developing cancer. However, the rate at which at-risk individuals undergo genetic evaluation is low, particularly for individuals that belong to populations that are historically underserved. We sought to characterize the demographic factors that may be associated with receipt of recommended HCS evaluation and follow-up. Methods: All patients with pathologically confirmed breast, ovarian, or fallopian tube cancers and qualifying for hereditary breast and ovarian cancer (HBOC) testing based on NCCN guidelines from 2016 to 2021 at an urban safety-net hospital were included in this analysis. Institutional review board approval was obtained. Demographic and oncologic data, as well as HBOC genetic testing outcomes were collected through retrospective chart review using a standardized data collection tool. Univariate logistic regression models were constructed to test the association of variables with receiving hereditary cancer genetic testing. Results: A total of 312 patients were included in the analysis, 90% of which had breast cancer. Forty percent were non-English speaking, 31% were non-White, and 25% were uninsured. Overall, 70% of patients were referred for genetic counseling and 65% underwent testing. Our analysis showed higher association of genetic testing uptake with Spanish language [odds ratio (95% confidence interval)] [1.74 (1.04, 2.93)], stage II disease [2.15 (1.11, 4.16)], and having a referral to genetic counseling [9.21 (5.32, 15.96)]. A lower rate of genetic testing was associated with patients identifying as Black [0.36 (1.87, 0.70)], having Medicare insurance [0.29 (0.14, 0.61)], a higher Charlson Comorbidity Index [0.31 (0.13, 0.73)], and older age [0.94 (0.92, 0.96)]. Uninsured patients had a similar association with genetic testing uptake as patients with Medicaid. Variables seeming to have no association with genetic testing uptake include family history of cancer, type of cancer, performance status, substance use, and Latinx ethnicity. A pathologic variant was found in 13% of our population. A variant of unknown significance (VUS) was found in 33% of Hispanic or Latinx patients and in 46% of non-Hispanic or Latinx patients who received testing, for a combined VUS prevalence of 39%. Conclusions: Our analysis shows that genetic testing rates for patients meeting HBOC syndrome criteria at an urban, safety-net institution were higher than expected, particularly for Spanish speaking patients and those with Medicaid or no insurance. We hypothesize this may be due to the emphasis our institution places on the care of uninsured patients through programs to make services accessible, as well as strong engagement with the Spanish speaking community. These results can help guide future interventions to target patient groups with lower rates of genetic testing, as well as maintain the successes seen among our diverse population.

7531 Background: Chimeric antigen receptor (CAR) T-cell therapy has improved the historically poor outcomes for relapsed and refractory (R/R) B-cell non-Hodgkin’s lymphoma (NHL). However, nearly 60% of patients will either fail to respond or relapse after CAR T-cell therapy. Currently, PET/CT scans are used to assess response. Cell-free circulating tumor DNA (ctDNA) is released by tumor cells into the peripheral blood and can be measured for minimal residual disease (MRD) assessment. Methods: In this retrospective, IRB approved pilot study, archived lymphoma tissues and ctDNA from peripheral blood samples on day 0, 14, 28, 56, 80, 180, and 365 after CAR T-cell infusion from 10 patients with R/R NHL were collected for next-generation sequencing (NGS) of clonal variable-diversity-joining (VDJ) rearrangements [Adaptive biotechnologies (Seattle, WA)]. Response was assessed by PET/CT on days 30, 60, 90, 180 and 365 and graded according to the Lugano 2014 criteria. The primary endpoint was to determine the feasibility of detecting ctDNA to monitor disease response after anti-CD19 CAR T-cells. The secondary endpoint was to compare the sensitivity/specificity of MRD assessment from ctDNA to PET/CT imaging. Results: Nine out of 10 patients with a trackable sequence [median age 69 (range: 56-76); 55.6% male; median LDH 224], were included in this study. Each received tisagenlecleucel CAR T-cell therapy after median two prior treatments (range: 2-4). 7/9 patients had R/R diffuse large B-cell lymphoma (DLBCL), and 2/9 had transformed follicular lymphoma. At a median follow up of 12.7 months (range: 1.5-30 months), four patients were alive. By day 90, three patients (33.3%) achieved a radiographic complete response (CR) whilst six patients (66.6%) had progressive disease (PD). MRD and radiographic response are outlined in the Table. Detectable MRD on day 14 or day 28 had 83% sensitivity and 100% specificity for radiographic progression at any time before one year. For patients with PD, the median (interquartile range) MRD at day 0, 14, and 28 were 17.31 (1.01, 96.84), 9.12 (0.30, 18.8), and 23.77 (8.01, 137.53) copies per milliliter (mL), respectively. For patients with detectable MRD at day 28, mOS and mPFS were 205 and 38 days, respectively. Conclusions: Our pilot study demonstrated that monitoring MRD was a sensitive and specific method to detect disease response and relapse. In addition, MRD can be monitored more frequently, thus allowing for earlier detection of relapse. MRD and PET/CT identified progressive disease (PD) or complete response (CR) by day 90 in nine patients (A-I) with R/R NHL post CAR T-cell infusion.[Table: see text]

Health disparities in low-income communities may be linked to residential exposures to chemicals infiltrating from the outdoors and characteristics of and sources in the home. Indoor sources comprise those introduced by the occupant as well as releases from building materials. To examine the impact of renovation on indoor pollutants levels and to classify chemicals by predominant indoor sources, we collected indoor air and surface wipes from newly renovated “green” low-income housing units in Boston before and after occupancy. We targeted nearly 100 semivolatile organic compounds (SVOCs) and volatile organic compounds (VOCs), including phthalates, flame retardants, fragrance chemicals, pesticides, antimicrobials, petroleum chemicals, chlorinated solvents, and formaldehyde, as well as particulate matter. All homes had indoor air concentrations that exceeded available risk-based screening levels for at least one chemical. We categorized chemicals as primarily influenced by the occupant or as having building-related sources. While building-related chemicals observed in this study may be specific to the particular housing development, occupant-related findings might be generalizable to similar communities. Among 58 detected chemicals, we distinguished 25 as primarily occupant-related, including fragrance chemicals 6-acetyl-1,1,2,4,4,7-hexamethyltetralin (AHTN) and 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta[g]-2-benzopyran (HHCB). The pre- to post-occupancy patterns of the remaining chemicals suggested important contributions from building materials for some, including dibutyl phthalate and xylene, whereas others, such as diethyl phthalate and formaldehyde, appeared to have both building and occupant sources. Chemical classification by source informs multi-level exposure reduction strategies in low-income housing. Keywords: Semivolatile organic compounds (SVOCs), Volatile organic compounds (VOCs), Indoor air, Surface wipes, Consumer products, Building materials

Green eco-friendly housing includes approaches to reduce indoor air pollutant sources and to increase energy efficiency. Although sealing/tightening buildings can save energy and reduce the penetration of outdoor pollutants, an adverse outcome can be increased buildup of pollutants with indoor sources. The objective of this study was to determine the differences in the indoor air quality (IAQ) between green and non-green homes in low-income housing complexes. In one housing complex, apartments were renovated using green principles (n=28). Home visits were conducted immediately after the renovation, and subsequently at 6 months and at 12 months following the renovation. Of these homes, eight homes had pre-renovation home visits; this allowed pre- and post-renovation comparisons within the same homes. Parallel visits were conducted in non-green (control) apartments (n=14) in a nearby low-income housing complex. The IAQ assessments included PM2.5, black carbon, ultrafine particles, sulfur, total volatile organic compounds (VOCs), formaldehyde, and air exchange rate. Data were analyzed using linear mixed-effects models. None of the indoor pollutant concentrations were significantly different between green and non-green homes. However, we found differences when comparing the concentrations before and after renovation. Measured immediately after renovation, indoor black carbon concentrations were significantly lower averaging 682 ng/m(3) in post-renovation vs. 2364 ng/m(3) in pre-renovation home visits (p=0.01). In contrast, formaldehyde concentrations were significantly higher in post-renovated (0.03 ppm) than in pre-renovated homes (0.01 ppm) (p=0.004). Questionnaire data showed that opening of windows occurred less frequently in homes immediately post-renovation compared to pre-renovation; this factor likely affected the levels of indoor black carbon (from outdoor sources) and formaldehyde (from indoor sources) more than the renovation status itself. To reduce IAQ problems and potentially improve health, careful selection of indoor building materials and ensuring sufficient ventilation are important for green building designs.

Background Adolescents and young adults (AYA), patients age 15‐39, may experience worse outcomes than pediatric and adult patients. The aim of this paper was to document survival disparities associated with insurance status across the AYA age continuum in the United States. Methods We utilized the Surveillance, Epidemiologic, and End Results database to identify 66 556 AYA patients between 2007 and 2014 with 10 International Classification of Childhood Cancer diagnoses and calculated the Cox proportional hazard ratios of death for those with public or no insurance status compared to private insurance. The odds ratios of having a late stage of diagnosis by insurance status were also calculated. Results Insurance status was a statistically significant predictor of death for lymphoid leukemia (age 15‐19, 30‐34, and 35‐39), acute myeloid leukemia (age 15‐19 and 25‐29), Hodgkin lymphoma (all ages), non‐Hodgkin lymphoma (age 20‐24, 25‐29, 30‐34, and 35‐39), astrocytomas (age 30‐34), other gliomas (age 25‐29, 30‐34, and 35‐39), hepatic carcinomas (age 25‐29), fibrosarcomas, peripheral nerve and other fibrous tumors (age 30‐34), malignant gonadal germ cell tumors (age 20‐24, 25‐29, 30‐34, and 35‐39), and other and unspecified carcinomas (age 20‐24, 25‐29, 30‐34, and 35‐39), independent of stage at diagnosis. This hazard increased with age for most cancer types. Insurance status strongly predicted the odds of a metastatic cancer diagnosis for lymphoma, fibrosarcomas (age 15‐19), germ cell tumors, and other carcinomas. Conclusions AYA in the US experience disparities in cancer survival based on insurance status, independent of late stage of presentation. Patients age 26‐39 may be especially vulnerable to health outcomes associated with poor socioeconomic status, treatment disparities, and poor access to care.

For many childhood cancers, survival is lower among non-Hispanic blacks and Hispanics in comparison with non-Hispanic whites, and this may be attributed to underlying socioeconomic factors. However, prior childhood cancer survival studies have not formally tested for mediation by socioeconomic status (SES). This study applied mediation methods to quantify the role of SES in racial/ethnic differences in childhood cancer survival.This study used population-based cancer survival data from the Surveillance, Epidemiology, and End Results 18 database for black, white, and Hispanic children who had been diagnosed at the ages of 0 to 19 years in 2000-2011 (n = 31,866). Black-white and Hispanic-white mortality hazard ratios and 95% confidence intervals, adjusted for age, sex, and stage at diagnosis, were estimated. The inverse odds weighting method was used to test for mediation by SES, which was measured with a validated census-tract composite index.Whites had a significant survival advantage over blacks and Hispanics for several childhood cancers. SES significantly mediated the race/ethnicity-survival association for acute lymphoblastic leukemia, acute myeloid leukemia, neuroblastoma, and non-Hodgkin lymphoma; SES reduced the original association between race/ethnicity and survival by 44%, 28%, 49%, and 34%, respectively, for blacks versus whites and by 31%, 73%, 48%, and 28%, respectively, for Hispanics versus whites ((log hazard ratio total effect - log hazard ratio direct effect)/log hazard ratio total effect).SES significantly mediates racial/ethnic childhood cancer survival disparities for several cancers. However, the proportion of the total race/ethnicity-survival association explained by SES varies between black-white and Hispanic-white comparisons for some cancers, and this suggests that mediation by other factors differs across groups.

Objectives. We examined associations of several health outcomes with green and conventional low-income housing, where the prevalence of morbidities and environmental pollutants is elevated. Methods. We used questionnaires and a visual inspection to compare sick building syndrome (SBS) symptoms and asthma-related morbidity among residents in multifamily units in Boston, Massachusetts, between March 2012 and May 2013. Follow-up was approximately 1 year later. Results. Adults living in green units reported 1.35 (95% confidence interval [CI] = 0.66, 2.05) fewer SBS symptoms than those living in conventional (control) homes (P Conclusions. Participants living in green homes had improved health outcomes, which remained consistent over the study period. Green housing may provide a significant value in resource-poor settings where green construction or renovation could simultaneously reduce harmful indoor exposures, promote resident health, and reduce operational costs.

Mitochondrial DNA (mtDNA) copy number is a critical component of overall mitochondrial health. In this chapter, we describe methods for simultaneous isolation of mtDNA and nuclear DNA (nucDNA), and measurement of their respective copy numbers using quantitative PCR. Methods differ depending on the species and cell type of the starting material, and availability of specific PCR reagents. We also briefly describe factors that affect mtDNA copy number and discuss caveats to its use as a biomarker.

Indoor air quality is an important predictor of health, especially in low-income populations. It is unclear how recent trends in "green" building affect the indoor exposure profile. In two successive years, we conducted environmental sampling, home inspections, and health questionnaires with families in green and conventional (control) apartments in two public housing developments. A subset of participants was followed as they moved from conventional to green or conventional to conventional housing. We measured particulate matter less than 2.5 μm aerodynamic diameter (PM2.5), formaldehyde, nitrogen dioxide (NO2), nicotine, carbon dioxide (CO2), and air exchange rate (AER) over a seven-day sampling period coincident with survey administration. In multivariate models, we observed 57%, 65%, and 93% lower concentrations of PM2.5, NO2, and nicotine (respectively) in green vs control homes (p=0.032, p

Parking lot runoff retention ponds (PLRRP) receive significant chemical input, but the biological effects of parking lot runoff are not well understood. We used the Japanese medaka (Oryzias latipes) as a model to study the toxicity of water and sediment samples from a PLRRP in Morehead City, NC. Medaka exposed in ovo to a dilution series of PLRRP water had increased odds of death before hatching, but not teratogenesis or delayed hatching. Next, we adapted a long-amplicon quantitative PCR (LA-QPCR) assay for DNA damage for use with the Japanese medaka. We employed LA-QPCR to test the hypotheses that PLRRP water and sediments would cause nuclear and mitochondrial DNA damage with and without full-spectrum, natural solar radiation. Fluoranthene with and without natural sunlight was a positive control for phototoxic polycyclic aromatic hydrocarbon-induced DNA damage. Fluoranthene exposure did not result in detectable DNA damage by itself, but in combination with sunlight caused significant DNA damage to both genomes. PLRRP samples caused DNA damage to both genomes, and this was not increased by sunlight exposure, suggesting the DNA damage was unlikely the result of PAH phototoxicity. We report for the first time that PLRRP-associated pollutants cause both nuclear and mitochondrial DNA damage, and that fluoranthene-mediated phototoxicity results in similar levels of damage to the nuclear and mitochondrial genomes. These effects may be especially significant in sensitive marine ecosystems.

Background: The fractional concentration of exhaled nitric oxide (FENO) is a non-invasive measure of poor asthma control. The indoor environment presents a complex array of pollutant exposures, whi...

6557Background: Disparities in cancer survival have been demonstrated between racial and ethnic groups. Several mechanisms could be involved, including differences in stage at presentation, treatme...