Immune checkpoint inhibitor (ICI) modality has had a limited success (<20%) in treating metastatic recurrent Head & Neck Oropharyngeal Squamous cell carcinomas (OPSCCs). To improve response rates to ICIs, tailored approaches capable to capture the tumor complexity and dynamics of each patient’s disease are needed. Here, we performed advanced analyses of spatial proteogenomic technologies to demonstrate that: (i) compared to standard histopathology, spatial transcriptomics better-identified tumor cells and could specifically classify them into two different metabolic states with therapeutic implications; (ii) our new method (Spatial Proteomics-informed cell deconvolution method or SPiD ) improved profiling of local immune cell types relevant to disease progression, (iii) identified clinically relevant alternative treatments and a rational explanation for checkpoint inhibitor therapy failure through comparative analysis of pre- and post-failure tumor data and, (iv) discovered ligand-receptor interactions as potential lead targets for personalized drug treatments. Our work establishes a clear path for incorporating spatial-omics in clinical settings to facilitate treatment personalization.

Vaccines have been hailed as one of the most remarkable medical advancements in human history, and their potential for treating cancer by generating or expanding anti-tumor T cells has garnered significant interest in recent years. However, the limited efficacy of therapeutic cancer vaccines in clinical trials can be partially attributed to the inadequacy of current preclinical mouse models in recapitulating the complexities of the human immune system. In this study, we developed two innovative humanized mouse models to assess the immunogenicity and therapeutic effectiveness of vaccines targeting human papillomavirus (HPV16) antigens and delivering tumor antigens to human CD141+ dendritic cells (DCs). Both models were based on the transference of human peripheral blood mononuclear cells (PBMCs) into immunocompromised HLA-A*02-NSG mice (NSG-A2), where the use of fresh PBMCs boosted the engraftment of human cells up to 80%. The dynamics of immune cells in the PBMC-hu-NSG-A2 mice demonstrated that T cells constituted the vast majority of engrafted cells, which progressively expanded over time and retained their responsiveness to ex vivo stimulation. Using the PBMC-hu-NSG-A2 system, we generated a hyperplastic skin graft model expressing the HPV16-E7 oncogene. Remarkably, human cells populated the skin grafts, and upon vaccination with a DNA vaccine encoding an HPV16-E6/E7 protein, rapid rejection targeted to the E7-expressing skin was detected, underscoring the capacity of the model to mount a vaccine-specific response. To overcome the decline in DC numbers observed over time in PBMC-hu-NSG-A2 animals, we augmented the abundance of CD141+ DCs, the specific targets of our tailored nanoemulsions (TNEs), by transferring additional autologous PBMCs pre-treated in vitro with the growth factor Flt3-L. The Flt3-L treatment bolstered CD141+ DC numbers, leading to potent antigen-specific CD4+ and CD8+ T cell responses in vivo, which caused the regression of pre-established triple-negative breast cancer and melanoma tumors following CD141+ DC-targeting TNE vaccination. Notably, using HLA-A*02-matching PBMCs for humanizing NSG-A2 mice resulted in a delayed onset of graft-versus-host disease and enhanced the efficacy of the TNE vaccination compared with the parental NSG strain. In conclusion, we successfully established two humanized mouse models that exhibited strong antigen-specific responses and demonstrated tumor regression following vaccination. These models serve as valuable platforms for assessing the efficacy of therapeutic cancer vaccines targeting HPV16-dysplastic skin and diverse tumor antigens specifically delivered to CD141+ DCs.

Immune checkpoint inhibitor (ICI) therapy has had limited success (<30%) in treating metastatic recurrent Head and Neck Oropharyngeal Squamous Cell Carcinomas (OPSCCs). We postulate that spatial determinants in the tumor play a critical role in cancer therapy outcomes. Here, we describe the case of a male patient diagnosed with p16+ OPSCC and extensive lung metastatic disease who failed Nivolumab and Pembrolizumab/Lenvatinib therapies. Using advanced integrative spatial proteogenomic analysis on the patient's recurrent OPSCC tumors we demonstrate that: (i) unbiased tissue clustering based on spatial transcriptomics (ST) successfully detected tumor cells and enabled the investigation of phenotypic traits such as proliferation or drug-resistance genes in the tumor's leading-edge and core; (ii) spatial proteomic imagining used in conjunction with ST (SpiCi, Spatial Proteomics inferred Cell identification) can resolve the profiling of tumor infiltrating immune cells, (iii) ST data allows for the discovery and ranking of clinically relevant alternative medicines based on their interaction with their matching ligand-receptor. Importantly, when the spatial profiles of ICI pre- and post-failure OPSCC tumors were compared, they exhibited highly similar PD-1/PD-L1low and VEGFAhigh expression, suggesting that these new tumors were not the product of ICI resistance but rather of Lenvatinib dose reduction due to complications. Our work establishes a path for incorporating spatial-omics in clinical settings to facilitate treatment personalization.

We study quantum dichotomies and the resource theory of asymmetric distinguishability using a generalization of Strassen's theorem on preordered semirings. We find that an asymptotic variant of relative submajorization, defined on unnormalized dichotomies, is characterized by real-valued monotones that are multiplicative under the tensor product and additive under the direct sum. These strong constraints allow us to classify and explicitly describe all such monotones, leading to a rate formula expressed as an optimization involving sandwiched Renyi divergences. As an application we give a new derivation of the strong converse error exponent in quantum hypothesis testing.

The development of cancer vaccines has been intensively pursued over the past 50 years with modest success. However, recent advancements in the fields of genetics, molecular biology, biochemistry, and immunology have renewed interest in these immunotherapies and allowed the development of promising cancer vaccine candidates. Numerous clinical trials testing the response evoked by tumour antigens, differing in origin and nature, have shed light on the desirable target characteristics capable of inducing strong tumour-specific non-toxic responses with increased potential to bring clinical benefit to patients. Novel delivery methods, ranging from a patient's autologous dendritic cells to liposome nanoparticles, have exponentially increased the abundance and exposure of the antigenic payloads. Furthermore, growing knowledge of the mechanisms by which tumours evade the immune response has led to new approaches to reverse these roadblocks and to re-invigorate previously suppressed anti-tumour surveillance. The use of new drugs in combination with antigen-based therapies is highly targeted and may represent the future of cancer vaccines. In this review, we address the main antigens and delivery methods used to develop cancer vaccines, their clinical outcomes, and the new directions that the vaccine immunotherapy field is taking.

ANZ Journal of SurgeryVolume 90, Issue 12 p. 2395-2396 PERSPECTIVES Time to harness ear, nose and throat surgeons' overwhelming support for increasing Aboriginal Torres Strait Islander outreach services Andrew Daniel MBBS, MIPH, Andrew Daniel MBBS, MIPH orcid.org/0000-0002-4302-6433 Department of Otolaryngology,The Children's Hospital in Westmead, Sydney, New South Wales, AustraliaSearch for more papers by this authorKelvin Kong BSc MBBS FRACS, Kelvin Kong BSc MBBS FRACS orcid.org/0000-0002-8384-0149 School of Medicine and Public Health, The University of Newcastle, Newcastle, New South Wales, Australia Department of Otolaryngology – Head and Neck Surgery, John Hunter Hospital, Sydney, New South Wales, AustraliaSearch for more papers by this authorChristopher Perry MBBS DTM&H FRACS, Christopher Perry MBBS DTM&H FRACS orcid.org/0000-0002-5484-7608 Department of Otolaryngology-Head and Neck Surgery, Princess Alexandra Hospital, Brisbane, Queensland, Australia Department of Otolaryngology-Head and Neck Surgery, Queensland Children's Hospital, Brisbane, Queensland, AustraliaSearch for more papers by this authorRobert Leonard Eisenberg MBBS FRACS, Robert Leonard Eisenberg MBBS FRACS School of Medicine and Public Health, The University of Newcastle, Newcastle, New South Wales, Australia Department of Otolaryngology – Head and Neck Surgery, John Hunter Hospital, Sydney, New South Wales, AustraliaSearch for more papers by this author Andrew Daniel MBBS, MIPH, Andrew Daniel MBBS, MIPH orcid.org/0000-0002-4302-6433 Department of Otolaryngology,The Children's Hospital in Westmead, Sydney, New South Wales, AustraliaSearch for more papers by this authorKelvin Kong BSc MBBS FRACS, Kelvin Kong BSc MBBS FRACS orcid.org/0000-0002-8384-0149 School of Medicine and Public Health, The University of Newcastle, Newcastle, New South Wales, Australia Department of Otolaryngology – Head and Neck Surgery, John Hunter Hospital, Sydney, New South Wales, AustraliaSearch for more papers by this authorChristopher Perry MBBS DTM&H FRACS, Christopher Perry MBBS DTM&H FRACS orcid.org/0000-0002-5484-7608 Department of Otolaryngology-Head and Neck Surgery, Princess Alexandra Hospital, Brisbane, Queensland, Australia Department of Otolaryngology-Head and Neck Surgery, Queensland Children's Hospital, Brisbane, Queensland, AustraliaSearch for more papers by this authorRobert Leonard Eisenberg MBBS FRACS, Robert Leonard Eisenberg MBBS FRACS School of Medicine and Public Health, The University of Newcastle, Newcastle, New South Wales, Australia Department of Otolaryngology – Head and Neck Surgery, John Hunter Hospital, Sydney, New South Wales, AustraliaSearch for more papers by this author First published: 17 December 2020 https://doi.org/10.1111/ans.16197Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume90, Issue12December 2020Pages 2395-2396 RelatedInformation

So-called Thermal Operations seem to describe the most fundamental and reasonable set of operations allowable for state transformations at an ambient inverse temperature β. However, a priori, they require experimentalists to manipulate very complex environments and have control over their internal degrees of freedom. For this reason, the community has been working on creating more experimentally-friendly operations. In [Perry, et al., Phys. Rev. X 8, 041049], it was shown that for states diagonal in the energy basis, Thermal Operations can be performed by so-called Coarse Operations, which need just one auxiliary qubit but are otherwise Markovian and classical in spirit. In this work, by providing an explicit counterexample, we show that this one qubit of memory is necessary. We also provide almost full characterization (i.e., full, but with one intriguing exception that remains open) of possible transitions that do not require memory in the case where the system is a qubit. We do this by analyzing arbitrary control sequences comprising level energy changes and partial thermalizations in each step.

Head and neck squamous cell carcinoma, and in particular hypopharyngeal squamous cell carcinoma, has long been associated with disfiguring treatment options, significant morbidity and limited long‐term survival outcomes. Total pharyngolaryngectomy (TPL) with free flap reconstruction followed by post‐operative radiation therapy or chemoradiotherapy is a widely accepted treatment of choice for advanced disease of the hypopharynx.

Pure state entanglement transformations have been thought of as irreversible, with reversible transformations generally only possible in the limit of many copies. Here, we show that reversible entanglement transformations do not require processing on the many copy level, but can instead be undertaken on individual systems, provided the amount of entanglement which is produced or consumed is allowed to fluctuate. We derive necessary and sufficient conditions for entanglement manipulations in this case. As a corollary, we derive an equation which quantifies the fluctuations of entanglement, which is formally identical to the Jarzynski fluctuation equality found in thermodynamics. One can also relate a forward entanglement transformation to its reverse process in terms of the entanglement cost of such a transformation, in a manner equivalent to the Crooks relation. We show that a strong converse theorem for entanglement transformations is formally related to the second law of thermodynamics, while the fact that the Schmidt rank of an entangled state cannot increase is related to the third law of thermodynamics. Achievability of the protocols is done by introducing an entanglement battery, a device which stores entanglement and uses an amount of entanglement that is allowed to fluctuate but with an average cost which is still optimal. This allows us to also solve the problem of partial entanglement recovery, and in fact, we show that entanglement is fully recovered. Allowing the amount of consumed entanglement to fluctuate also leads to improved and optimal entanglement dilution protocols.

Heat-Bath Algorithmic Cooling is a set of techniques for producing highly pure quantum systems by utilizing a surrounding heat-bath and unitary interactions. These techniques originally used the thermal environment only to fully thermalize ancillas at the environment temperature. Here we extend HBAC protocols by optimizing over the thermalization strategy. We find, for any d-dimensional system in an arbitrary initial state, provably optimal cooling protocols with surprisingly simple structure and exponential convergence to the ground state. Compared to the standard ones, these schemes can use fewer or no ancillas and exploit memory effects to enhance cooling. We verify that the optimal protocols are robusts to various deviations from the ideal scenario. For a single target qubit, the optimal protocol can be well approximated with a Jaynes-Cummings interaction between the system and a single thermal bosonic mode for a wide range of environmental temperatures. This admits an experimental implementation close to the setup of a micromaser, with a performance competitive with leading proposals in the literature. The proposed protocol provides an experimental setup that illustrates how non-Markovianity can be harnessed to improve cooling. On the technical side we 1. introduce a new class of states called maximallyactivestates and discuss their thermodynamic significance in terms of optimal unitary control, 2. introduce a new set of thermodynamic processes, called β-permutations, whose access is sufficient to simulate a generic thermalization process, 3. show how to use abstract toolbox developed within the resource theory approach to thermodynamics to perform challenging optimizations, while combining it with open quantum system dynamics tools to approximate optimal solutions within physically realistic setups.

Pure state entanglement transformations have been thought of as irreversible, with reversible transformations generally only possible in the limit of many copies. Here, we show that reversible entanglement transformations do not require processing on the many copy level, but can instead be undertaken on individual systems, provided the amount of entanglement which is produced or consumed is allowed to fluctuate. We derive necessary and sufficient conditions for entanglement manipulations in this case. As a corollary, we derive an equation which quantifies the fluctuations of entanglement, which is formally identical to the Jarzynski fluctuation equality found in thermodynamics. One can also relate a forward entanglement transformation to its reverse process in terms of the entanglement cost of such a transformation, in a manner equivalent to the Crooks relation. We show that a strong converse theorem for entanglement transformations is formally related to the second law of thermodynamics, while the fact that the Schmidt rank of an entangled state cannot increase is related to the third law of thermodynamics. Achievability of the protocols is done by introducing an entanglement battery, a device which stores entanglement and uses an amount of entanglement that is allowed to fluctuate but with an average cost which is still optimal. This allows us to also solve the problem of partial entanglement recovery, and in fact, we show that entanglement is fully recovered. Allowing the amount of consumed entanglement to fluctuate also leads to improved and optimal entanglement dilution protocols.

We show that any unital qubit channel can be implemented by letting the input system interact unitarily with a four-dimensional environment in the maximally mixed state and then tracing out the environment. We also provide an example where the dimension of such an environment has to be at least 3.

Heat-Bath Algorithmic Cooling is a technique for producing pure quantum systems by utilizing a surrounding heat-bath. Here we connect the study of these cooling techniques to the resource theory of thermal operations, enabling us to derive provably optimal cooling protocols under a variety of experimental restrictions on the available control. For qubit systems, we find that a surprisingly simple, optimal protocol consisting of repeated application of a Pauli $X$ unitary and a thermal operation can achieve purity converging exponentially quickly to one. What is more, this thermal operation can be well approximated using a Jaynes Cummings interaction between the system and a single thermal bosonic mode and we consider experimental implementations of this. In addition, we investigate the role of quantum coherence and non-Markovianity in cooling protocols and extend our results to higher dimensional systems. Finally, by considering the role of correlations with auxiliary systems in cooling, we show that purity arbitrary close to one can be achieved in a fixed number of operations. Our results serve to find practical applications for the resource theoretic approach to quantum thermodynamics and suggest relevant experimental implementations.

To what extent do thermodynamic resource theories capture physically relevant constraints? Inspired by quantum computation, we define a set of elementary thermodynamic gates that only act on 2 energy levels of a system at a time. We show that this theory is well reproduced by a Jaynes-Cummings interaction in rotating wave approximation and draw a connection to standard descriptions of thermalisation. We then prove that elementary thermal operations present tighter constraints on the allowed transformations than thermal operations. Mathematically, this illustrates the failure at finite temperature of fundamental theorems by Birkhoff and Muirhead-Hardy-Littlewood-Polya concerning stochastic maps. Physically, this implies that stronger constraints than those imposed by single-shot quantities can be given if we tailor a thermodynamic resource theory to the relevant experimental scenario. We provide new tools to do so, including necessary and sufficient conditions for a given change of the population to be possible. As an example, we describe the resource theory of the Jaynes-Cummings model. Finally, we initiate an investigation into how our resource theories can be applied to Heat Bath Algorithmic Cooling protocols.

Recent work using tools from quantum information theory has shown that at the nanoscale where quantum effects become prevalent, there is not one thermodynamical second law but many. Derivations of these laws assume that an experimenter has very precise control of the system and heat bath. Here we show that these multitude of laws can be saturated using two very simple operations: changing the energy levels of the system and thermalizing over any two system energy levels. Using these two operations, one can distill the optimal amount of work from a system, as well as perform the reverse formation process. Even more surprisingly, using only these two operations and one ancilla qubit in a thermal state, one can transform any state into any other state allowable by the second laws. We thus have the remarkable result that the second laws hold for fine-grained manipulation of system and bath, but can be achieved using very coarse control. This brings the full array of thermal operations into a regime accessible by experiment, and establishes the physical relevance of these second laws.

By how much must the communication complexity of a function increase if we demand that the parties not only correctly compute the function but also return all registers (other than the one containing the answer) to their initial states at the end of the communication protocol? Protocols that achieve this are referred to as clean and the associated cost as the clean communication complexity. Here we present clean protocols for calculating the inner product of two n-bit strings, showing that (in the absence of preshared entanglement) at most n+3 qubits or n+O(sqrt[n]) bits of communication are required. The quantum protocol provides inspiration for obtaining the optimal method to implement distributed cnot gates in parallel while minimizing the amount of quantum communication. For more general functions, we show that nearly all Boolean functions require close to 2n bits of classical communication to compute and close to n qubits if the parties have access to preshared entanglement. Both of these values are maximal for their respective paradigms.

If the second law of thermodynamics forbids a transition from one state to another, then it is still possible to make the transition happen by using a sufficient amount of work. But if we do not have access to this amount of work, can the transition happen probabilistically? In the thermodynamic limit, this probability tends to zero, but here we find that for finite-sized and quantum systems it can be finite. We compute the maximum probability of a transition or a thermodynamical fluctuation from any initial state to any final state and show that this maximum can be achieved for any final state that is block diagonal in the energy eigenbasis. We also find upper and lower bounds on this transition probability, in terms of the work of transition. As a by-product, we introduce a finite set of thermodynamical monotones related to the thermomajorization criteria which governs state transitions and compute the work of transition in terms of them. The trade-off between the probability of a transition and any partial work added to aid in that transition is also considered. Our results have applications in entanglement theory, and we find the amount of entanglement required (or gained) when transforming one pure entangled state into any other.

We prove the existence of (one-way) communication tasks with a subconstant versus superconstant asymptotic gap, which we call "doubly infinite," between their quantum information and communication complexities. We do so by studying the exclusion game [C. Perry et al., Phys. Rev. Lett. 115, 030504 (2015)] for which there exist instances where the quantum information complexity tends to zero as the size of the input n increases. By showing that the quantum communication complexity of these games scales at least logarithmically in n, we obtain our result. We further show that the established lower bounds and gaps still hold even if we allow a small probability of error. However in this case, the n-qubit quantum message of the zero-error strategy can be compressed polynomially.

Summary of results for the detection of HPV-16-specific DNA and RNA in oral rinse of patients with p16INK4a-positive HNSCC (XLSX 41Â kb)

We investigate the connection between recent results in quantum thermodynamics and fluctuation relations by adopting a fully quantum mechanical description of thermodynamics. By including a work system whose energy is allowed to fluctuate, we derive a set of equalities that all thermodynamical transitions have to satisfy. This extends the condition for maps to be Gibbs preserving to the case of fluctuating work, providing a more general characterization of maps commonly used in the information theoretic approach to thermodynamics. For final states, block diagonal in the energy basis, this set of equalities is a necessary and sufficient condition for a thermodynamical state transition to be possible. The conditions serve as a parent equation that can be used to derive a number of results. These include writing the second law of thermodynamics as an equality featuring a fine-grained notion of the free energy. It also yields a generalization of the Jarzynski fluctuation theorem which holds for arbitrary initial states, and under the most general manipulations allowed by the laws of quantum mechanics. Furthermore, we show that each of these relations can be seen as the quasiclassical limit of three fully quantum identities. This allows us to consider the free energy as an operator, and allows one to obtain more general and fully quantum fluctuation relations from the information theoretic approach to quantum thermodynamics.