SUMMARY It has long been thought that clonal deletion efficiently removes almost all self-specific T cells from the peripheral repertoire. But here we found that self peptide-MHC specific CD8+ T cells in the blood of healthy humans were present in frequencies similar to those specific for non-self antigens. For the Y chromosome encoded SMCY antigen, self-specific T cells exhibited only a three-fold lower average frequency in males versus females and were anergic with respect to peptide activation, although this inhibition could be overcome by a stronger stimulus. We conclude that clonal deletion prunes but does not eliminate self-specific T cells and suggest that to do so would create holes in the repertoire that pathogens could readily exploit. In support of this hypothesis, we detected T cells specific for all 20 amino acid variants at the p5 position of a hepatitis C virus epitope in a random group of blood donors.

A systems analysis of immune biomarkers in 89 young and older adults revealed age-dependent and age-independent features, including markers of apoptosis that correlated with antibody responses to a seasonal influenza vaccine.

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Background In lung cancer, brain metastases (BM) and their treatment are associated with high economic burden and inferior health‐related quality of life. In the era of targeted therapy, real world evidence through health utility scores (HUS) is critical for economic analyses. Materials and Methods In a prospective observational cohort study (2014–2016), outpatients with stage IV lung cancer completed demographic and EQ‐5D‐3L surveys (to derive HUS). Health states and clinicopathologic variables were obtained from chart abstraction. Patients were categorized by the presence or absence of BM; regression analyses identified factors that were associated with HUS. A subset of patients prospectively completed neurocognitive function (NCF) tests and/or the FACT‐brain (FACT‐Br) questionnaire, which were then correlated with HUS (Spearman coefficients; regression analyses). Results Of 519 patients with 1,686 EQ‐5D‐3L‐derived HUS, 94 (18%) completed NCF tests and 107 (21%) completed FACT‐Br; 301 (58%) never developed BM, 24 (5%) developed first BM during study period, and 194 (37%) had BM at study entry. The sample was enriched (46%) for EGFR mutations (EGFRm) and ALK‐rearrangements (ALKr). There were no HUS differences by BM status overall and in subsets by demographics. In multivariable analyses, superior HUS was associated with having EGFRm/ALKr (p < .0001), no prior radiation for extracranial disease (p < .001), and both intracranial (p = .002) and extracranial disease control (p < .01). HUS correlated with multiple elements of the FACT‐Br and tests of NCF. Conclusion Having BM in lung cancer is not associated with inferior HUS in a population enriched for EGFRm and ALKr. Patients exhibiting disease control and those with oncogene‐addicted tumors have superior HUS. Implications for Practice In the setting of EGFR mutations or ALK rearrangement non‐small cell lung cancer (NSCLC), a diagnosis of brain metastases no longer consigns the patient to an inferior health state suggesting that new economic analyses in NSCLC are needed in the era of targeted therapies. Additionally, the EQ‐5D questionnaire is associated with measures of health‐related quality of life and neurocognitive scores suggesting this tool should be further explored in prospective clinical studies.

Analysis of B and T cell responses in non-small cell lung cancer (NSCLC) patients enrolled in a phase II trial of cyclophosphamide with allogenic DRibble vaccine (DPV-001