The expanded role of the transplant pharmacist: A 10-year follow-up.

The role of the transplant pharmacist is recognized by transplant programs, governmental groups, and professional organizations as an essential part of the transplant multidisciplinary team. This role has evolved drastically over the last decade with the advent of major advances in the science of transplantation and the growth of the field, which necessitate expanded pharmacy services to meet the needs of patients. Data now exist within all realms of the phases of care for a transplant recipient regarding the utility and benefit of a solid organ transplant (SOT) pharmacist. Furthermore, governing bodies now have the opportunity to use Board Certification in Solid Organ Transplant Pharmacotherapy as a mechanism to identify and recognize specialty knowledge and expertise within the field of SOT pharmacotherapy. The purpose of this paper is to provide an overarching review of the current and future state of SOT pharmacy while also identifying major changes to the profession, forthcoming challenges, and expected areas of growth.

Individuals with mild-to-moderate hip osteoarthritis walk with lower hip joint contact forces despite higher levels of muscle co-contraction compared to healthy individuals.

OBJECTIVE: To compare hip joint contact forces (HJCF), hip muscle forces, and hip muscle co-contraction levels between individuals with mild-to-moderate hip osteoarthritis (OA) and healthy controls during walking. DESIGN: Eighteen participants with mild-to-moderate hip OA and 23 healthy controls walked at a self-selected speed while motion capture and electromyographic data were synchronously collected. HJCF were computed using a calibrated electromyography-informed neuromusculoskeletal model. Hip joint contact forces, muscle forces, and co-contraction indices for flexor/extensor and adductor/abductor muscle groups were compared between groups using independent sample t-tests (P < 0.05). RESULTS: There was no between-group difference in self-selected walking speed. On average, participants with hip OA walked with 11% lower first peak (mean difference 235 [95% confidence interval (CI) 57-413] N) and 22% lower second peak (mean difference 574 [95%CI 304-844] N) HJCF compared to controls. Hip muscle forces were also significantly lower in the hip OA compared to control group at first (mean difference 224 [95%CI 66-382] N) and second (mean difference 782 [95%CI 399-1164] N) peak HJCF. Participants with hip OA exhibited higher levels of hip muscle co-contraction in both flexor/extensor and adductor/abductor muscle groups. Consistent with existing literature, hip joint angles (extension, adduction) and external moments (flexion, extension, adduction) were lower in hip OA compared to controls. CONCLUSION: Lower HJCF were detected in mild-to-moderate hip OA, primarily due to lower hip muscle force production, and despite higher levels of hip muscle co-contraction. Findings suggest that lower loading of the hip joint during walking is a feature of mild-to-moderate hip OA, which could have implications for the pathogenesis of hip OA and/or disease progression.

Epigenetics in natural animal populations.

Phenotypic plasticity is an important mechanism for populations to buffer themselves from environmental change. While it has long been appreciated that natural populations possess genetic variation in the extent of plasticity, a surge of recent evidence suggests that epigenetic variation could also play an important role in shaping phenotypic responses. Compared with genetic variation, epigenetic variation is more likely to have higher spontaneous rates of mutation and a more sensitive reaction to environmental inputs. In our review, we first provide an overview of recent studies on epigenetically encoded thermal plasticity in animals to illustrate environmentally-mediated epigenetic effects within and across generations. Second, we discuss the role of epigenetic effects during adaptation by exploring population epigenetics in natural animal populations. Finally, we evaluate the evolutionary potential of epigenetic variation depending on its autonomy from genetic variation and its transgenerational stability. Although many of the causal links between epigenetic variation and phenotypic plasticity remain elusive, new data has explored the role of epigenetic variation in facilitating evolution in natural populations. This recent progress in ecological epigenetics will be helpful for generating predictive models of the capacity of organisms to adapt to changing climates.

Heritable gene expression differences between lake and stream stickleback include both parallel and antiparallel components.

The repeated phenotypic patterns that characterize populations undergoing parallel evolution provide support for a deterministic role of adaptation by natural selection. Determining the level of parallelism also at the genetic level is thus central to our understanding of how natural selection works. Many studies have looked for repeated genomic patterns in natural populations, but work on gene expression is less common. The studies that have examined gene expression have found some support for parallelism, but those studies almost always used samples collected from the wild that potentially confounds the effects of plasticity with heritable differences. Here we use two independent pairs of lake and stream threespine stickleback (Gasterosteus aculeatus) raised in common garden conditions to assess both parallel and antiparallel (that is, similar versus different directions of lake-stream expression divergence in the two watersheds) heritable gene expression differences as measured by total RNA sequencing. We find that more genes than expected by chance show either parallel (22 genes, 0.18% of expressed genes) or antiparallel (24 genes, 0.20% of expressed genes) lake-stream expression differences. These results correspond well with previous genomic studies in stickleback ecotype pairs that found similar levels of parallelism. We suggest that parallelism might be similarly constrained at the genomic and transcriptomic levels.

Admixture on the northern front: population genomics of range expansion in the white-footed mouse (Peromyscus leucopus) and secondary contact with the deer mouse (Peromyscus maniculatus).

Range expansion has genetic consequences expected to result in differentiated wave-front populations with low genetic variation and potentially introgression from a local species. The northern expansion of Peromyscus leucopus in southern Quebec provides an opportunity to test these predictions using population genomic tools. Our results show evidence of recent and post-glacial expansion. Genome-wide variation in P. leucopus indicates two post-glacial lineages are separated by the St. Lawrence River, with a more recent divergence of populations isolated by the Richelieu River. In two of three transects we documented northern populations with low diversity in at least one genetic measure, although most relationships were not significant. Consistent with bottlenecks and allele surfing during northward expansion, we document a northern-most population with low nucleotide diversity, divergent allele frequencies and the most private alleles, and observed heterozygosity indicates outcrossing. Ancestry proportions revealed putative hybrids of P. leucopus and P. maniculatus. A formal test for gene flow confirmed secondary contact, showing that a reticulate population phylogeny between P. maniculatus and P. leucopus was a better fit to the data than a bifurcating model without gene flow. Thus, we provide the first genomic evidence of gene flow between this pair of species in natural populations. Understanding the evolutionary consequences of secondary contact is an important conservation concern as climate-induced range expansions are expected to result in new hybrid zones between closely related species.

Impact of a pharmacist-led vaccine recommendation program for pediatric kidney transplant candidates.

Pediatric transplant recipients commonly have deficient vaccination status at the time of transplantation. Utilizing transplant pharmacists to improve vaccination rates has not previously been described. This single-center, retrospective study evaluated the impact of transplant pharmacist interventions on the completion rate of vaccination schedules at time of kidney transplant. Patients who received pharmacist-led vaccination recommendations prior to transplant were compared to patients without pharmacist recommendations. Forty-seven pediatric patients were included: 24 intervention patients and 23 control patients. The median percentage of up-to-date vaccinations at time of transplant was significantly higher in intervention group (91%; IQR 86%-100%) vs. control group (80%; IQR 71%-80%) (P<.0001). The median change in up-to-date vaccinations from time of evaluation to time of transplant was also significantly higher in the intervention group (7.5%) compared to the control group (0%) (P<.0001). There was no difference in live vaccination rates. No patients in either group were readmitted for a vaccine-preventable disease within 6 months post-transplant. With pharmacist intervention, significantly more patients were up to date with vaccination schedules at the time of transplant. These results suggest that a transplant pharmacist may serve as a valuable resource to increase vaccination schedule compliance between time of evaluation and transplantation.

Regional three-dimensional deformation of human Achilles tendon during conditioning.

Our understanding of in vivo Achilles tendon (AT) conditioning is limited to two-dimensional ultrasound measures of longitudinal deformation of the whole tendon. This study investigated the regional three-dimensional (3D) deformation of the AT during conditioning. Eighteen ATs were scanned using 3D freehand ultrasound during 10 successive 25 s submaximal (50%) voluntary isometric plantarflexion contractions. Longitudinal strain was assessed for the whole AT, aponeurosis, and free AT and transverse strain was assessed for the proximal-, mid-, and distal-portions of the free AT. Longitudinal conditioning of the whole AT was primarily driven by creep response of the free AT and transverse conditioning was greatest for the mid-portion of the free AT. Whole and free AT longitudinal strain increased up to the third contraction and were accompanied by a corresponding reduction in free AT cross-sectional area (CSA) strain in proximal-, mid-, and distal-portions. No significant changes in aponeurosis strain or tendon volume were detected between contractions. These findings suggest that conditioning alters free AT shape, with increased tendon length attained at the expense of reduction in free AT CSA. Although AT experiences different amounts of strain in different regions, the number of contractions required to reach steady-state strain during conditioning is uniform throughout the tendon.

In vivo strain in the deep and superficial regions of the human patellar tendon.

This study investigated strain differences within the patellar tendon (PT) mid-region using an ultrasound-based digital image correlation (DIC) method. Six healthy young participants performed six knee extensions to 60% of maximal voluntary isometric contraction on 2 days. Sagittal ultrasound videos recorded during each contraction were analyzed using the DIC method to determine the strain-torque relationships of the superficial, deep, and whole PT mid-regions. Significantly greater strain was observed in the deep vs superficial layer of the PT mid-region for all contraction intensities, with peak strains of 5.8% (SD 1.7) and 4.5% (SD 1.5), respectively. DIC-based measures of peak tendon strain were repeatable within [intraclass coefficients (ICC) >0.97] and between sessions (ICCs >0.83) and agreed well with the conventional point-to-point method. This study confirmed that significant differences exist between deep and superficial layers of PT mid-region during ramped isometric extensions. These findings support the use of DIC to examine regional strain patterns within the PT mid-region that may be important in the context of tendon injury and adaptation.

Testing for parallel allochronic isolation in lake-stream stickleback.

The evolution of reproductive isolation (RI) is a critical step shaping progress towards speciation. In the context of ecological speciation, a critical question is the extent to which specific reproductive barriers important to RI evolve rapidly and predictably in response to environmental differences. Only reproductive barriers with these properties (importance, rapidity, predictability) will drive the diversification of species that are cohesively structured by environment type. One candidate barrier that might exhibit such properties is allochrony, whereby populations breed at different times. We studied six independent lake-stream population pairs of threespine stickleback (Gasterosteus aculeatus Linnaeus, 1758) that are known from genetic studies to show RI. However, the specific reproductive barriers driving this RI have proven elusive, leading to a 'conundrum of missing reproductive isolation'. We here show that breeding times differ among some of the populations, but not in a consistent manner between lakes and streams. Moreover, the timing differences between lake and stream populations within each pair could account for only a small proportion of total RI measured with neutral genetic markers. Allochrony cannot solve the conundrum of missing reproductive isolation in lake-stream stickleback.

Assessing reproductive isolation using a contact zone between parapatric lake-stream stickleback ecotypes.

Ecological speciation occurs when populations evolve reproductive isolation as a result of divergent natural selection. This isolation can be influenced by many potential reproductive barriers, including selection against hybrids, selection against migrants and assortative mating. How and when these barriers act and interact in nature is understood for relatively few empirical systems. We used a mark-recapture experiment in a contact zone between lake and stream three-spined sticklebacks (Gasterosteus aculeatus, Linnaeus) to evaluate the occurrence of hybrids (allowing inferences about mating isolation), the interannual survival of hybrids (allowing inferences about selection against hybrids) and the shift in lake-like vs. stream-like characteristics (allowing inferences about selection against migrants). Genetic and morphological data suggest the occurrence of hybrids and no selection against hybrids in general, a result contradictory to a number of other studies of sticklebacks. However, we did find selection against more lake-like individuals, suggesting a barrier to gene flow from the lake into the stream. Combined with previous work on this system, our results suggest that multiple (most weakly and often asymmetric) barriers must be combining to yield substantial restrictions on gene flow. This work provides evidence of a reproductive barrier in lake-stream sticklebacks and highlights the value of assessing multiple reproductive barriers in natural contexts.

Hemostatic Matrix (FloSeal) as Treatment for Urethral Crush Injury After Failure of Traditional Hemostatic Technique.

We report a case of traumatic arterial hemorrhage from the posterior urethral artery, refractory to traditional hemostatic technique, and successfully managed with intraurethral thrombin hemostatic matrix (FloSeal [Baxter Healthcare Corporation, Deerfield, Illinois, US]). We believe that this demonstrates a safe, effective therapy for urethral hemorrhage that may be accomplished by Emergency Physicians and may preclude the need for more invasive hemorrhage control strategies.

Changes in Achilles tendon mechanical properties following eccentric heel drop exercise are specific to the free tendon.

Mechanical loading of the Achilles tendon during isolated eccentric contractions could induce immediate and region-dependent changes in mechanical properties. Three-dimensional ultrasound was used to examine the immediate effect of isolated eccentric exercise on the mechanical properties of the distal (free tendon) and proximal (gastrocnemii) regions of the Achilles tendon. Participants (n = 14) underwent two testing sessions in which tendon measurements were made at rest and during a 30% and 70% isometric plantar flexion contractions immediately before and after either: (a) 3 × 15 eccentric heel drops or (b) 10-min rest. There was a significant time-by-session interaction for free tendon length and strain for all loading conditions (P < 0.05). Pairwise comparisons revealed a significant increase in free tendon length and strain at all contraction intensities after eccentric exercise (P < 0.05). There was no significant time-by-session interaction for the gastrocnemii (medial or lateral) aponeurosis or tendon for any of the measured parameters. Immediate changes in Achilles tendon mechanical properties were specific to the free tendon and consistent with changes due to mechanical creep. These findings suggest that the mechanical properties of the free tendon may be more vulnerable to change with exercise compared with the gastrocnemii aponeurosis or tendon.

Targeting pili in enterococcal pathogenesis.

Passive protection, the administration of antibodies to prevent infection, has garnered significant interest in recent years as a potential prophylactic countermeasure to decrease the prevalence of hospital-acquired infections. Pili, polymerized protein structures covalently anchored to the peptidoglycan wall of many Gram-positive pathogens, are ideal targets for antibody intervention, given their importance in establishing infection and their accessibility to antibody interactions. In this work, we demonstrated that a monoclonal antibody to the major component of Enterococcus faecalis pili, EbpC, labels polymerized pilus structures, diminishes biofilm formation, and significantly prevents the establishment of a rat endocarditis infection. The effectiveness of this anti-EbpC monoclonal provides strong evidence in support of its potential as a preventative. In addition, after radiolabeling, this monoclonal identified the site of enterococcal infection, providing a rare example of molecularly specific imaging of an established bacterial infection and demonstrating the versatility of this agent for use in future diagnostic and therapeutic applications.

Library screen identifies Enterococcus faecalis CcpA, the catabolite control protein A, as an effector of Ace, a collagen adhesion protein linked to virulence.

The Enterococcus faecalis cell wall-anchored protein Ace is an important virulence factor involved in cell adhesion and infection. Expression of Ace on the cell surface is affected by many factors, including stage of growth, culture temperature, and environmental components, such as serum, urine, and collagen. However, the mechanisms that regulate or modulate Ace display are not well understood. With interest in identifying genes associated with Ace expression, we utilized a whole-cell enzyme-linked immunosorbent assay (ELISA)-based screening method to identify mutants from a transposon insertion mutant library which exhibited distinct Ace surface expression profiles. We identified a ccpA insertion mutant which showed significantly decreased levels of Ace surface expression at early growth phase versus those of wild-type OG1RF. Confirmation of the observation was achieved through flow cytometry and complementation analysis. Compared to the wild type, the E. faecalis ccpA mutant had an impaired ability to adhere to collagen when grown to early exponential phase, consistent with the lack of Ace expression in the early growth phase. As a key component of carbon catabolite regulation, CcpA has been previously reported to play a critical role in regulating expression of proteins involved in E. faecalis carbohydrate uptake and utilization. Our discovery is the first to associate CcpA with the production of a major E. faecalis virulence factor, providing new insights into the regulation of E. faecalis pathogenesis.

Genetic suppression of the circadian Clock mutation by the melatonin biosynthesis pathway.

Most laboratory mouse strains including C57BL/6J do not produce detectable levels of pineal melatonin owing to deficits in enzymatic activity of arylalkylamine N-acetyltransferase (AANAT) and N-acetylserotonin O-methyl transferase (ASMT), two enzymes necessary for melatonin biosynthesis. Here we report that alleles segregating at these two loci in C3H/HeJ mice, an inbred strain producing melatonin, suppress the circadian period-lengthening effect of the Clock mutation. Through a functional mapping approach, we localize mouse Asmt to chromosome X and show that it, and the Aanat locus on chromosome 11, are significantly associated with pineal melatonin levels. Treatment of suprachiasmatic nucleus (SCN) explant cultures from Period2(Luciferase) (Per2(Luc)) Clock/+ reporter mice with melatonin, or the melatonin agonist, ramelteon, phenocopies the genetic suppression of the Clock mutant phenotype observed in living animals. These results demonstrate that melatonin suppresses the Clock/+ mutant phenotype and interacts with Clock to affect the mammalian circadian system.

Fungal Planet description sheets: 154-213.

Novel species of microfungi described in the present study include the following from South Africa: Camarosporium aloes, Phaeococcomyces aloes and Phoma aloes from Aloe, C. psoraleae, Diaporthe psoraleae and D. psoraleae-pinnatae from Psoralea, Colletotrichum euphorbiae from Euphorbia, Coniothyrium prosopidis and Peyronellaea prosopidis from Prosopis, Diaporthe cassines from Cassine, D. diospyricola from Diospyros, Diaporthe maytenicola from Maytenus, Harknessia proteae from Protea, Neofusicoccum ursorum and N. cryptoaustrale from Eucalyptus, Ochrocladosporium adansoniae from Adansonia, Pilidium pseudoconcavum from Greyia radlkoferi, Stagonospora pseudopaludosa from Phragmites and Toxicocladosporium ficiniae from Ficinia. Several species were also described from Thailand, namely: Chaetopsina pini and C. pinicola from Pinus spp., Myrmecridium thailandicum from reed litter, Passalora pseudotithoniae from Tithonia, Pallidocercospora ventilago from Ventilago, Pyricularia bothriochloae from Bothriochloa and Sphaerulina rhododendricola from Rhododendron. Novelties from Spain include Cladophialophora multiseptata, Knufia tsunedae and Pleuroascus rectipilus from soil and Cyphellophora catalaunica from river sediments. Species from the USA include Bipolaris drechsleri from Microstegium, Calonectria blephiliae from Blephilia, Kellermania macrospora (epitype) and K. pseudoyuccigena from Yucca. Three new species are described from Mexico, namely Neophaeosphaeria agaves and K. agaves from Agave and Phytophthora ipomoeae from Ipomoea. Other African species include Calonectria mossambicensis from Eucalyptus (Mozambique), Harzia cameroonensis from an unknown creeper (Cameroon), Mastigosporella anisophylleae from Anisophyllea (Zambia) and Teratosphaeria terminaliae from Terminalia (Zimbabwe). Species from Europe include Auxarthron longisporum from forest soil (Portugal), Discosia pseudoartocreas from Tilia (Austria), Paraconiothyrium polonense and P. lycopodinum from Lycopodium (Poland) and Stachybotrys oleronensis from Iris (France). Two species of Chrysosporium are described from Antarctica, namely C. magnasporum and C. oceanitesii. Finally, Licea xanthospora is described from Australia, Hypochnicium huinayensis from Chile and Custingophora blanchettei from Uruguay. Novel genera of Ascomycetes include Neomycosphaerella from Pseudopentameris macrantha (South Africa), and Paramycosphaerella from Brachystegia sp. (Zimbabwe). Novel hyphomycete genera include Pseudocatenomycopsis from Rothmannia (Zambia), Neopseudocercospora from Terminalia (Zambia) and Neodeightoniella from Phragmites (South Africa), while Dimorphiopsis from Brachystegia (Zambia) represents a novel coelomycetous genus. Furthermore, Alanphillipsia is introduced as a new genus in the Botryosphaeriaceae with four species, A. aloes, A. aloeigena and A. aloetica from Aloe spp. and A. euphorbiae from Euphorbia sp. (South Africa). A new combination is also proposed for Brachysporium torulosum (Deightoniella black tip of banana) as Corynespora torulosa. Morphological and culture characteristics along with ITS DNA barcodes are provided for all taxa.

Disentangling the Impact of Point Defect Density and Carrier Localization-Enhanced Auger Recombination on Efficiency Droop in (In,Ga)N/GaN Quantum Wells.

The internal quantum efficiency of (In,Ga)N/GaN quantum wells can surpass 90% for blue-emitting structures at moderate drive current densities but decreases significantly for longer emission wavelengths and at higher excitation rates. This latter effect is known as efficiency "droop" and limits the brightness of light-emitting diodes (LEDs) based on such quantum wells. Several mechanisms have been proposed to explain efficiency droop including Auger recombination, both intrinsic and defect-assisted, carrier escape, and the saturation of localized states. However, it remains unclear which of these mechanisms is most important because it has proven difficult to reconcile theoretical calculations of droop with measurements. Here, we first present experimental photoluminescence measurements extending over three orders of magnitude of excitation for three samples grown at different temperatures that indicate that droop behavior is not dependent on the point defect density in the quantum wells studied. Second, we use an atomistic tight-binding electronic structure model to calculate localization-enhanced radiative and Auger rates and show that both the corresponding carrier density-dependent internal quantum efficiency and the carrier density decay dynamics are in excellent agreement with our experimental measurements. Moreover, we show that point defect density, Auger recombination, and the effect of the polarization field on recombination rates only limit the peak internal quantum efficiency to about 70% in the resonantly excited green-emitting quantum wells studied. This suggests that factors external to the quantum wells, such as carrier injection efficiency and homogeneity, contribute appreciably to the significantly lower peak external quantum efficiency of green LEDs.

The community engagement course and action network: strengthening community and academic research partnerships to advance health equity.

Background: Historically Black Colleges and Universities and Minority Serving Institutions are uniquely positioned to implement community-campus research partnerships based on a history of service, the pursuit of community trustworthiness and student demographics often similar to surrounding marginalized communities. The Morehouse School of Medicine Prevention Research Center collaborates with members of Historically Black Colleges and Universities, Minority Serving Institutes, and community organizations on the Community Engaged Course and Action Network. This network is the first of its kind and aims to strengthen members' ability to implement Community-Based Participatory Research (CBPR) principles and partnerships. Projects address public health priorities including mental health among communities of color, zoonotic disease prevention, and urban food deserts. Materials and methods: To assess the effectiveness of the network, a Participatory Evaluation framework was implemented to conduct process evaluation which included review of partnership structures, operations, project implementation processes, and preliminary outcomes of the research collaborations. A focus group of Community Engagement Course and Action Network members (community and academic) was also conducted to identify benefits and challenges of the network with emphasis on key areas for improvement to further enhance the relationships between partners and to facilitate their subsequent community-campus research. Results: Network improvements were tied to themes strengthening community-academic partnerships including sharing and fellowship, coalition building and collaboration, and greater connections and awareness of community needs through their current community-academic partnerships. The need to conduct ongoing evaluation during and after implementation, for determining the early adoption of CBPR approaches was also identified. Conclusion: Evaluation of the network's processes, infrastructure, and operation provides early lessons learned to strengthen the network. Ongoing assessment is also essential for ensuring continuous quality improvement across partnerships such as determining CBPR fidelity, assessing partnership synergy, and dynamics, and for quality improvement of research protocol. The implications and potential for advancing implementation science through this and similar networks are great towards advancing leadership in modeling how foundations in community service can advance to CBPR partnership formation and ultimately, health equity approaches, that are local defined and assessed.

Immune Cell Abundance and T-cell Receptor Landscapes Suggest New Patient Stratification Strategies in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a molecularly and spatially heterogeneous disease frequently characterized by impairment of immunosurveillance mechanisms. Despite recent success with immunotherapy treatment, disease progression still occurs quickly after treatment in the majority of cases, suggesting the need to improve patient selection strategies. In the quest for biomarkers that may help inform response to checkpoint blockade, we characterized the tumor microenvironment (TME) of 162 HNSCC primary tumors of diverse etiologic and spatial origin, through gene expression and IHC profiling of relevant immune proteins, T-cell receptor (TCR) repertoire analysis, and whole-exome sequencing. We identified five HNSCC TME categories based on immune/stromal composition: (i) cytotoxic, (ii) plasma cell rich, (iii) dendritic cell rich, (iv) macrophage rich, and (v) immune-excluded. Remarkably, the cytotoxic and plasma cell rich subgroups exhibited a phenotype similar to tertiary lymphoid structures (TLS), which have been previously linked to immunotherapy response. We also found an increased richness of the TCR repertoire in these two subgroups and in never smokers. Mutational patterns evidencing APOBEC activity were enriched in the plasma cell high subgroup. Furthermore, specific signal propagation patterns within the Ras/ERK and PI3K/AKT pathways associated with distinct immune phenotypes. While traditionally CD8/CD3 T-cell infiltration and immune checkpoint expression (e.g., PD-L1) have been used in the patient selection process for checkpoint blockade treatment, we suggest that additional biomarkers, such as TCR productive clonality, smoking history, and TLS index, may have the ability to pull out potential responders to benefit from immunotherapeutic agents. SIGNIFICANCE: Here we present our findings on the genomic and immune landscape of primary disease in a cohort of 162 patients with HNSCC, benefitting from detailed molecular and clinical characterization. By employing whole-exome sequencing and gene expression analysis of relevant immune markers, TCR profiling, and staining of relevant proteins involved in immune response, we highlight how distinct etiologies, cell intrinsic, and environmental factors combine to shape the landscape of HNSCC primary disease.