The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.

Molecular dynamics simulations have to be sufficiently long to draw reliable conclusions. However, no method exists to prove that a simulation has converged. We suggest the method of “lagged RMSD-analysis” as a tool to judge if an MD simulation has not yet run long enough. The analysis is based on RMSD values between pairs of configurations separated by variable time intervals Δt. Unless RMSD(Δt) has reached a stationary shape, the simulation has not yet converged.

Solutions to the Thirring model are constructed in the framework of algebraic quantum field theory. It is shown that for all positive temperatures there are fermionic solutions only if the coupling constant is λ = 2(2n + 1)π, n ∈ N. These fermions are inequivalent and only for n = 1 they are canonical fields. In the general case solutions are anyons. Different anyons (which are uncountably many) live in orthogonal spaces and obey dynamical equations (of the type of Heisenberg's "Urgleichung") characterized by the corresponding values of the statistic parameter. Thus statistic parameter turns out to be related to the coupling constant λ and the whole Hilbert space becomes non-separable with a different "Urgleichung" satisfied in each of its sectors. This feature certainly cannot be seen by any power expansion in λ. Moreover, since the latter is tied to the statistic parameter, it is clear that such an expansion is doomed to failure and will never reveal the true structure of the theory.The correlation functions in the temperature state for the canonical dressed fermions are shown by us to coincide with the ones for the bare fields, that is in agreement with the uniqueness of the τ -KMS state over the CAR algebra (τ being the shift automorphism). Also the α-anyon two-point function is evaluated and for scalar field it reproduces the result that is known from the literature.It is an honour for us to present this paper to the 30 th anniversary of "Theoretical and Mathematical Physics". With its scientific reputation and high standards the journal takes a valuable place in the heritage of its founder, N.N. Bogoliubov -one of the outstanding scientists of this century, and we wish this to be kept also in the future.

Our objective is to reveal the molecular mechanism of the anti-inflammatory action of low-molecular-weight heparin (LMWH) based on its influence on the activity of two key cytokines, IFNγ and IL-6. The mechanism of heparin binding to IFNγ and IL-6 and the resulting inhibition of their activity were studied by means of extensive molecular-dynamics simulations. The effect of LMWH on IFNγ signalling inside stimulated WISH cells was investigated by measuring its antiproliferative activity and the translocation of phosphorylated STAT1 in the nucleus. We found that LMWH binds with high affinity to IFNγ and is able to fully inhibit the interaction with its cellular receptor. It also influences the biological activity of IL-6 by binding to either IL-6 or IL-6/IL-6Rα, thus preventing the formation of the IL-6/IL-6Rα/gp130 signalling complex. These findings shed light on the molecular mechanism of the anti-inflammatory action of LMWH and underpin its ability to influence favourably conditions characterised by overexpression of these two cytokines. Such conditions are not only associated with autoimmune diseases, but also with inflammatory processes, in particular with COVID-19. Our results put forward heparin as a promising means for the prevention and suppression of severe CRS and encourage further investigations on its applicability as an anti-inflammatory agent.