Type III interferon inhibits bladder cancer progression by reprogramming macrophage-mediated phagocytosis and orchestrating effective immune responses.

BACKGROUND: Interferons (IFNs) are essential for activating an effective immune response and play a central role in immunotherapy-mediated immune cell reactivation for tumor regression. Type III IFN (λ), related to type I IFN (α), plays a crucial role in infections, autoimmunity, and cancer. However, the direct effects of IFN-λ on the tumor immune microenvironment have not been thoroughly investigated. METHODS: We used mouse MB49 bladder tumor models, constructed a retroviral vector expressing mouse IFN-λ3, and transduced tumor cells to evaluate the antitumor action of IFN-λ3 in immune-proficient tumors and T cell-deficient tumors. Furthermore, human bladder cancer samples (cohort 1, n=15) were used for immunohistochemistry and multiplex immunoflurescence analysis to assess the expression pattern of IFN-λ3 in human bladder cancer and correlate it with immune cells' infiltration. Immunohistochemistry analysis was performed in neoadjuvant immunotherapy cohort (cohort 2, n=20) to assess the correlation between IFN-λ3 expression and the pathological complete response rate. RESULTS: In immune-proficient tumors, ectopic Ifnl3 expression in tumor cells significantly increased the infiltration of cytotoxic CD8+ T cells, Th1 cells, natural killer cells, proinflammatory macrophages, and dendritic cells, but reduced neutrophil infiltration. Transcriptomic analyses revealed significant upregulation of many genes associated with effective immune response, including lymphocyte recruitment, activation, and phagocytosis, consistent with increased antitumor immune infiltrates and tumor inhibition. Furthermore, IFN-λ3 activity sensitized immune-proficient tumors to anti-PD-1/PD-L1 blockade. In T cell-deficient tumors, increased Ly6G-Ly6C+I-A/I-E+ macrophages still enhanced tumor cell phagocytosis in Ifnl3 overexpressing tumors. IFN-λ3 is expressed by tumor and stromal cells in human bladder cancer, and high IFN-λ3 expression was positively associated with effector immune infiltrates and the efficacy of immune checkpoint blockade therapy. CONCLUSIONS: Our study indicated that IFN-λ3 enables macrophage-mediated phagocytosis and antitumor immune responses and suggests a rationale for using Type III IFN as a predictive biomarker and potential immunotherapeutic candidate for bladder cancer.

Low in-band spurious arbitrary waveform generator based on a 1-bit time-wavelength interleaved photonic digital-to-analog conversion.

We proposed an arbitrary waveform generator based on a 1-bit photonic digital-to-analog conversion (PDAC). The system is based on the principle of photonic pulse sampling and time interleaving. High-speed optical pulses are generated and modulated by digital signals and then synthesized in one path. The analog signals are obtained by an optical-to-electrical conversion of the time-interleaved pulses. Due to the 1-bit structure, there are no spurious components in principle. In the experiment, a 1-bit PDAC of 50 GSa/s is realized, and the X-band linear frequency-modulated (LFM) waveform with a bandwidth of 4 GHz is generated, the signal-to-spur-rejection ratio is as high as 50 dB, and the millimeter-wave 64QAM signal is generated, with an EVM of 4.27%.

Random code shifting based ultra-wideband photonic compressive receiver with image-frequency distinction.

We propose an ultra-wideband photonic compressive receiver based on random codes shifting with image-frequency distinction. By shifting the center frequencies of two random codes in large frequency range, the receiving bandwidth is flexibly expanded. Simultaneously, the center frequencies of two random codes are slightly different. This difference is used to distinguish the "fixed" true RF signal from the differently located image-frequency signal. Based on this idea, our system solves the problem of limited receiving bandwidth of existing photonic compressive receivers. In the experiments, with two channels of only 780-MHz outputs, the sensing capability in the range of 11-41 GHz has been demonstrated. A multi-tone spectrum and a sparse radar-communication spectrum, composed of a linear frequency modulated (LFM) signal, a quadrature phase-shift keying (QPSK) signal and a single-tone signal, are both recovered.

Dispersion-less Kerr solitons in spectrally confined optical cavities.

Solitons are self-reinforcing localized wave packets that manifest in the major areas of nonlinear science, from optics to biology and Bose-Einstein condensates. Recently, optically driven dissipative solitons have attracted great attention for the implementation of the chip-scale frequency combs that are decisive for communications, spectroscopy, neural computing, and quantum information processing. In the current understanding, the generation of temporal solitons involves the chromatic dispersion as a key enabling physical effect, acting either globally or locally on the cavity dynamics in a decisive way. Here, we report on a novel class of solitons, both theoretically and experimentally, which builds up in spectrally confined optical cavities when dispersion is practically absent, both globally and locally. Precisely, the interplay between the Kerr nonlinearity and spectral filtering results in an infinite hierarchy of eigenfunctions which, combined with optical gain, allow for the generation of stable dispersion-less dissipative solitons in a previously unexplored regime. When the filter order tends to infinity, we find an unexpected link between dissipative and conservative solitons, in the form of Nyquist-pulse-like solitons endowed with an ultra-flat spectrum. In contrast to the conventional dispersion-enabled nonlinear Schrödinger solitons, these dispersion-less Nyquist solitons build on a fully confined spectrum and their energy scaling is not constrained by the pulse duration. Dispersion-less soliton molecules and their deterministic transitioning to single solitons are also evidenced. These findings broaden the fundamental scope of the dissipative soliton paradigm and open new avenues for generating soliton pulses and frequency combs endowed with unprecedented temporal and spectral features.

Photonic-assisted space-frequency two-dimensional compressive radar receiver for high-resolution and wide-range detection.

Existing photonic compressive receivers have the problem of resolution deterioration when applied in wide-range radar detection. In this study, we propose a photonic-assisted space-frequency two-dimensional (2D) compressive radar receiver capable of achieving high-resolution detection in wide-range scenarios. For the space dimension, the compression process is realized by employing a spatially adaptive photonic projection basis, which guarantees complete mapping of arbitrarily delayed echoes-the key to high-resolution wide-range detection. For the frequency dimension, photonic compressive sensing is employed to further compress the bandwidth of the projected sparse signal. Therefore, the proposed system can achieve wide-range radar detection without resolution deterioration with compressed output. Herein, with two channels of 630 MHz outputs, high-resolution distance detection within a range of 21 km with a resolution of up to 2.3 cm is achieved. Moreover, inverse synthetic aperture radar (ISAR) imaging of two sets of four-point turntables distributed within the range of 21 km with a resolution of 2.3 cm × 5.7 cm is realized. The proposed photonic-assisted 2D compressive radar receiver is a viable solution to overcome the tradeoff between detection resolution and range of existing photonic compressive receivers, which indicates a path for the further development of high-resolution wide-range radar detection.

Tunable K/W-band OFDM integrated radar and communication system based on optoelectronic oscillator for intelligent transportation.

In this paper, we proposed a tunable K/W-band OFDM integrated radar and communication system based on Optoelectronic Oscillator (OEO) for intelligent transportation. All-optical signal processing including amplitude asymmetric filtering and quadratic phase manipulating is applied in OEO to achieve a high-frequency and tunable self-excited oscillation, which supports the K/W-band OFDM signal generation. Its product of maximum detection range and communication capacity is cB/4Δf (m·Gbaud), where c is light speed and Δf is subcarrier spacing of OFDM. A proof-of-concept experiment is carried out in K-band with bandwidth B = 2 GHz and W-band with bandwidth B = 10 GHz. The range resolution ΔR, detection range Rmax and communication capacity C of 0.075 m, 75 m, 12.8 Gbps, and 0.015 m, 300 m, 32 Gbps are experimentally demonstrated in K/W-band respectively.

Negative Effects of Stromal Neutrophils on T Cells Reduce Survival in Resectable Urothelial Carcinoma of the Bladder.

Urothelial carcinoma of the bladder (UCB) is a major type of bladder cancer with a distinct tumor microenvironment (TME). Although neutrophils are the main component of myeloid cells in the TME, the clinical significance and function of the neutrophils remain unclear in UCB. Here, we observed CD66b+ neutrophils were predominantly enriched in the stroma of UCB tissues and their levels emerged as an independent prognostic factor for overall survival (P = 0.006, n = 237), and were positively associated with age (P = 0.033), tumor stage (P < 0.0001), nodal metastasis (P = 0.045), and histological grade (P < 0.0001). Furthermore, we found that CD66b+ neutrophils were frequently co-localized with CD4+ T cells (R=0.35, P = 0.0067), CD8+ T cells (R=0.52, P<0.0001) and Cleaved Caspase-3+ apoptosis cells (R=0.44, P = 0.0007) in the stroma of UCB tissue. In addition, better effects of T cells on patients' survival were markedly reduced by neutrophils and T cells co-infiltration. Moreover, we confirmed bladder tumor cell supernatant treated neutrophils suppressed T cell proliferation and activation, and promoted T cell apoptosis through GM-CSF induced PD-L1 in vitro. The expression of PD-L1 by neutrophils was also detected in fresh UCB tissues by using flow cytometric analysis. These data suggested that stromal CD66b+ neutrophils may potentially represent a reliable marker of poor prognosis for UCB patients, and neutrophils might play an immunosuppressive role on T cell immunity partially via the expression of PD-L1.

Photonics-assisted joint radar and communication system based on an optoelectronic oscillator.

This paper reports a photonics-assisted joint radar and communication system for intelligent transportation based on an optoelectronic oscillator (OEO). By manipulating the optical multi-dimensional processing module inserted in the OEO loop, two phase-orthogonal integrated signals are generated with low phase noise and high frequency, as the communication data loaded on the overall polarity of radar pulses. At the receiver, single-channel matched filtering and two-channel IQ data fusion are utilized to retrieve the communication data and the range profile, without any performance deterioration of either. In this way, the contradiction between the performance of two functions existing in the previous scheme is solved, and the integrated performance can be further optimized as bandwidth increases. A proof-of-concept experiment with 2 GHz bandwidth at 24 GHz, which is the operating frequency of short-range automotive radar, is carried out to verify that the proposed system can meet the requirement of the intelligent vehicles in the short-range scene. A communication capacity of 335.6 Mbps, a range profile with a resolution of 0.075 m, and a peak-to-sidelobe ratio (PSLR) of 20 dB is demonstrated under the experimental condition. The error vector magnitude (EVM) curve and constellation diagrams versus received power are measured, where the EVM is -8 and -14.5 dB corresponding to a power of -14 and 6 dBm, respectively.

Development and validation of a PD-L1/PD-1/CD8 axis-based classifier to predict cancer survival of upper tract urothelial carcinoma after radical nephroureterectomy.

The expression status of programmed cell death-ligand 1/programmed cell death 1 (PD-L1/PD-1) and the infiltration of CD8+ T cells in tumor tissues are considered to be related to immunotherapy efficacy and patient prognosis. The purpose of this study is to clarify the prognostic value of the PD-L1/PD-1/CD8 axis, and to develop and validate a comprehensive scoring system based on multiple immune variables to predict cancer survival of upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). The immunohistochemical method was used to detect the expression of PD-L1, PD-1, and CD8 in cancer tissues of UTUC patients after RNU. Then, an immunoscore was constructed using the least absolute shrinkage and selection operator (LASSO) Cox regression model in the training cohort (n = 120), and it was verified in the validation cohort (n = 54). We found that infiltration of PD-L1+ immune cells (ICs), stromal PD-1+ tumor-infiltrating lymphocytes (TILs), and intratumoral CD8+ TILs was associated with poor overall survival (OS). The immunoscore based on the three immune variables further divided the patients into low- and high-risk groups, and there was a significant difference in the survival rate. A nomogram was constructed by combining tumor-node-metastasis (TNM) stage and immunoscore, and the area under the curve of the receiver-operating characteristic (ROC) (0.78) for predicting 5-year mortality was better than that of the TNM stage (0.70) and immunoscore (0.76). Our results show that the PD-L1/PD-1/CD8 axis-based classifier have potential clinical application to predict cancer survival of UTUC patients after RNU.

High-resolution W-band ISAR imaging system utilizing a logic-operation-based photonic digital-to-analog converter.

W-band inverse synthetic aperture radar (ISAR) imaging systems are very useful for automatic target recognition and classification due to their high spatial resolution, high penetration and small antenna size. Broadband linear frequency modulated wave (LFMW) is usually applied to this system for its de-chirping characteristic. However, nearly all of the LFMW generated in electronic W-band ISAR system are based on multipliers and mixers, suffering seriously from electromagnetic interference (EMI) and timing jitter. And photonic-assisted LFMW generator reported before is always limited by bandwidth or time aperture. In this paper, for the first time, we propose and experimentally demonstrate a high-resolution W-band ISAR imaging system utilizing a novel logic-operation-based photonic digital-to-analog converter (LOPDAC). The equivalent sampling rate of the LOPDAC is twice as large as the rate of the digital driving signal. Thus, a broadband LFMW with a large time aperture can be generated by the LOPDAC. This LFMW is up-converted to W band with an optical frequency comb. After photonic-assisted de-chirping processing and data processing to the echo, a high-resolution two-dimension image can be obtained. Experimentally, W-band radar with a time-bandwidth product (TBWP) as large as 79200 (bandwidth 8 GHz; temporal duration 9.9 us) is established and investigated. Results show that the two-dimension (range and cross-range) imaging resolution is ~1.9 cm × ~1.6 cm with a sampling rate of 100 MSa/s in the receiver.

Photonics-based wideband distributed coherent aperture radar system.

A photonics-based wideband distributed coherent aperture radar (DCAR) system is proposed and experimentally demonstrated. In the proposed system, the central controlling system and several spatially dispersed remote transceivers are connected by the optical fiber-based time synchronization network. In the central controlling system, the optical-carried orthogonal/coherent linear frequency modulated waveforms (LFMWs) are generated by a reconfigurable multi-channel optical arbitrary waveform generator (RMOAWG), and the signal processing for the echo waves is also implemented there. While in the remote transceivers, only the optical/RF and RF/optical conversions are carried out. Benefitting from the use of photonics-based methods, bandwidths of the generated radar signals can be large, improving the detection resolution of the system. Due to the centralized signal generation and processing, the remote transceivers can be simplified, reducing the system complexity. Moreover, the fiber-based distribution ensures low loss, good transportability, and great flexibility. Experimentally, a two-unit DCAR system operating in X-band with a bandwidth of 3 GHz is presented. When full coherence is achieved, signal-to-noise ratio (SNR) gains of 8.3 dB and 8.33 dB are obtained over a single radar for radar 1 and radar 2, respectively. Results are in good agreement with theoretical prediction. Theoretically, with such SNR gain, the range detection precision can be improved to about 2.6 times that of a single radar.

In-service crosstalk monitoring, tracing and lightpath re-optimization for space-division multiplexing optical networks.

In recent years, to enlarge the single-mode fibers (SMFs) transmission capacity, researchers focused on the dimension of space, which is a new degree of freedom that is being considered for optical fiber communication beyond WDM. Space-division multiplexing (SDM), including mode-division multiplexing (MDM) using multimode fibers (MMFs) or few-mode fibers (FMFs), and core multiplexing using multicore fibers (MCFs), has attracted much recent attention. In an SDM system, high-density spatial channels are tightly packed into a single fiber, thus making crosstalk among cores or modes a critical challenge due to fiber imperfections, bending, and twisting. Previous studies have mostly been confined to the routing algorithms for crosstalk reduction but few focuses on the in-service crosstalk monitoring, tracing and quality-of-transmission (QoT)-oriented lightpath re-optimization. In this paper, we proposed novel in-service crosstalk monitoring and tracing (CMT) method and algorithm using fine-grained optical time slice monitoring channels for crosstalk reduction in SDM optical networks. Benefitting from the large amount of fine-grained channels provided by optical time slices, it becomes possible for every source node to allocate a dedicated monitoring time slice carrying the traffic and path information for each connection. Crosstalk monitoring and tracing can be realized by extracting the information contained in these monitoring time slices. Simulation results shows that the proposed CMT method and algorithm can obtain acceptable performance in large-scale network scenarios. Furthermore, we also proposed a quality-of-transmission (QoT)-oriented lightpath re-optimization mechanism based on in-service crosstalk monitoring and tracing to maintain a high level of QoT. Finally, we designed a prototype experiment to validate our proposed in-service crosstalk monitoring method. Results show that this method can realize in-service crosstalk monitoring, tracing and lightpath re-optimization over a seven-core fiber based transmission system, and the crosstalk with a minimum value of -37.9 dB can be monitored and successfully traced.

Photonic generation of multi-frequency phase-coded microwave signal based on a dual-output Mach-Zehnder modulator and balanced detection.

A photonic scheme to generate a multi-frequency phase-coded microwave signal based on a dual-output Mach-Zehnder modulator (DOMZM) and balanced detection is proposed in this paper. The DOMZM driven by an electrical coding data modulates a coherent multi-wavelength light source (CMWL), and a balanced photodetector (BPD) demodulates the output of the DOMZM; as a result, a multi-frequency phase-coded microwave signal is generated. Experiments generate two two-frequency phase-coded signals: one is 5GHz/10GHz signal with a coding rate of 2Gb/s, and the other is 10GHz/20GHz signal with a coding rate of 4Gb/s. Their autocorrelation results show a good pulse compression capability. Each frequency of a two-frequency signal has similar performances with the other in terms of peak-to-side lobe ratio (PSR) and the full width at half-maximum (FWHM) of the main lobe. The proposed scheme can be applied to radar to reduce false detections in adverse conditions. With its potential flexible frequency agility, it can be used for jamming resistance and elimination of the Doppler blind speed during moving target detection.

Tunable dual frequency optoelectronic oscillator with low intermodulation based on dual-parallel Mach-Zehnder modulator.

A tunable dual-frequency optoelectronic oscillator (OEO) based on dual-parallel Mach-Zehnder modulator (DPMZM) with low intermodulation is proposed and experimentally demonstrated. Two tunable electronic band-pass filters are used to select the oscillation modes of the two oscillating frequencies to achieve tunable dual-frequency OEO (TDF-OEO). Each of the two selected modes are modulated onto one sub-modulator of the DPMZM. By choosing proper bias conditions of the DPMZM, the intermodulation components generated by the dual-frequencies are suppressed. The tuning range of the TDF-OEO is from 1 GHz to 15 GHz in the experiment. We also discussed and experimentally demonstrated the tuning limitation of this dual frequency system.

Tunable microwave photonic notch filter based on sliced broadband optical source.

A microwave photonic filter is demonstrated with both tunable center frequency and bandwidth. This filter is switchable from all-pass, bandpass to notch filter, and the notch filter is a result of the subtraction of a bandpass filter from an all-pass filter based on a balanced photodetector. The all-pass filter is achieved based on a single wavelength radio over fiber link, and the bandpass one is acquired by using the spectrum-sliced broadband optical source. Theoretical analysis and experimental results show that both the center frequency and the bandwidth of the notch filter can be widely tuned.

High-efficiency microwave photonic harmonic down-conversion with tunable and reconfigurable filtering.

A new optical-frequency comb-based microwave photonic harmonic down-convertor with tunable and reconfigurable filtering is proposed and experimentally demonstrated. The coherent evenly spaced optical carriers offer harmonic down-conversion for ultrahigh radio frequency signals with low-frequency local oscillator, and construct a tunable and reconfigurable bandpass filter for the intermediate-frequency (IF) signal combined with dispersion. This implementation features high conversion efficiency. Experimental results show the filtered output IF signal has a clean spectrum with high quality. Measured conversion loss is 8.3 dB without extra electrical amplification.

Ultra-flat optical frequency comb generator using a single-driven dual-parallel Mach-Zehnder modulator.

We propose and experimentally demonstrate a simple and cost-effective ultra-flat optical frequency comb (OFC) generator by directly modulating a standalone dual-parallel Mach-Zehnder modulator (DP-MZM) with only one radio frequency (RF) signal without any other assisting devices. Five- and seven-tone OFC with exactly the same intensity can be theoretically generated using two sets of parameters obtained by solving equations derived from the DP-MZM modulation model. In good agreement with the theoretical results, five- and seven-tone OFC with flatness of 0.1 and 1 dB are experimentally demonstrated, respectively.

Idler-free microwave photonic mixer integrated with a widely tunable and highly selective microwave photonic filter.

A novel structure consisting of an idler-free microwave photonic mixer integrated with a widely tunable and highly selective microwave photonic filter is presented, which is comprised of a spectrum-sliced broadband optical source, a dual-parallel Mach-Zehnder modulator (DPMZM), and a spatial light amplitude and phase processor (SLAPP). By adjusting the optical phase shift in the DPMZM, the dispersion-induced mixing power fading can be eliminated. By applying a phase processor with the SLAPP, the distortion of the mixing filter brought upon by third-order dispersion is also compensated. Experiments are performed and show that the up/down-conversion signal has a clean spectrum and the mixing filter can be tuned from 12 to 20 GHz without any change to the passband shape. The out-of-band suppression ratio of the mixing filter is more than 40 dB, and the 3 dB bandwidth is 140 MHz.

Gaussian-like dual-wavelength prescaled clock recovery with simultaneous frequency-doubled clock recovery using an optoelectronic oscillator.

A novel multifunctional frequency-doubling optoelectronic oscillator (FD-OEO) mainly based on a Mach-Zehnder modulator (MZM) cascaded with a phase modulator (PM) and a subsequent optical bandpass filter (OBPF) is proposed. We experimentally demonstrate simultaneous operations of frequency-doubled optical clock (FD-OC) recovery, low-duty-cycle dual-wavelength prescaled OC recovery and error-free fourfold time division demultiplexing with the proposed OEO injected with a 4 × 25-Gb/s optical time-division-multiplexing (OTDM) signal. We show that the proposed FD-OEO operates well for both the differential phase shift keying (DPSK) and on-off keying (OOK) modulation formats. The extracted dual-wavelength prescaled OC is proved to be nearly transform-limited with Gaussian-like shape. Furthermore, all four 25-Gb/s tributaries can be selectively demultiplexed by adjusting the phase shifters in the OEO loop. The power penalty at a bit error rate (BER) of 10(-9) is measured to be 2.4 dB, 1.2 dB for the best channel for DPSK signal and to be 2.5 dB, 1.1 dB for the best channel for OOK signal. In addition, as an extra benefit of the OEO, low-phase-noise prescaled electrical clock (EC) is also extracted.

Pair-by-pair pulse shaping for optical arbitrary waveform generation by dual-comb heterodyne.

We present a novel optical arbitrary waveform generation approach based on pair-by-pair pulse shaping. Based on the heterodyne between a pair of optical frequency combs with different repetition rates, the repetition rate of the generated signals can be flexibly tuned from MHz to GHz without changing the setup. The restriction of the spectral resolution of the optical spectrum processor is overcome by the pair-by-pair approach while the spectral resolution of the system can be improved to MHz by dual-comb heterodyne. Hyperfine control of a higher resolution spectrum at MHz is achieved, which benefits the generation of the ultrawideband signals.