In situ tumour arrays reveal early environmental control of cancer immunity.

The immune phenotype of a tumour is a key predictor of its response to immunotherapy1-4. Patients who respond to checkpoint blockade generally present with immune-inflamed5-7 tumours that are highly infiltrated by T cells. However, not all inflamed tumours respond to therapy, and even lower response rates occur among tumours that lack T cells (immune desert) or that spatially exclude T cells to the periphery of the tumour lesion (immune excluded)8. Despite the importance of these tumour immune phenotypes in patients, little is known about their development, heterogeneity or dynamics owing to the technical difficulty of tracking these features in situ. Here we introduce skin tumour array by microporation (STAMP)-a preclinical approach that combines high-throughput time-lapse imaging with next-generation sequencing of tumour arrays. Using STAMP, we followed the development of thousands of arrayed tumours in vivo to show that tumour immune phenotypes and outcomes vary between adjacent tumours and are controlled by local factors within the tumour microenvironment. Particularly, the recruitment of T cells by fibroblasts and monocytes into the tumour core was supportive of T cell cytotoxic activity and tumour rejection. Tumour immune phenotypes were dynamic over time and an early conversion to an immune-inflamed phenotype was predictive of spontaneous or therapy-induced tumour rejection. Thus, STAMP captures the dynamic relationships of the spatial, cellular and molecular components of tumour rejection and has the potential to translate therapeutic concepts into successful clinical strategies.

G protein-coupled estrogen receptor 1 ameliorates nonalcoholic steatohepatitis through targeting AMPK-dependent signaling.

Nonalcoholic fatty liver disease (NAFLD), especially nonalcoholic steatohepatitis (NASH), has emerged as a prevalent cause of liver cirrhosis and hepatocellular carcinoma, posing severe public health challenges worldwide. The incidence of NASH is highly correlated with an increased prevalence of obesity, insulin resistance, diabetes, and other metabolic diseases. Currently, no approved drugs specifically targeted for the therapies of NASH partially due to the unclear pathophysiological mechanisms. G protein-coupled estrogen receptor 1 (GPER1) is a membrane estrogen receptor involved in the development of metabolic diseases such as obesity and diabetes. However, the function of GPER1 in NAFLD/NASH progression remains unknown. Here, we show that GPER1 exerts a beneficial role in insulin resistance, hepatic lipid accumulation, oxidative stress, or inflammation in vivo and in vitro. In particular, we observed that the lipid accumulation, inflammatory response, fibrosis, or insulin resistance in mouse NAFLD/NASH models were exacerbated by hepatocyte-specific GPER1 knockout but obviously mitigated by hepatic GPER1 activation in female and male mice. Mechanistically, hepatic GPER1 activates AMP-activated protein kinase signaling by inducing cyclic AMP release, thereby exerting its protective effect. These data suggest that GPER1 may be a promising therapeutic target for NASH.

Electrochemical Late-Stage Functionalization.

Late-stage functionalization (LSF) constitutes a powerful strategy for the assembly or diversification of novel molecular entities with improved physicochemical or biological activities. LSF can thus greatly accelerate the development of medicinally relevant compounds, crop protecting agents, and functional materials. Electrochemical molecular synthesis has emerged as an environmentally friendly platform for the transformation of organic compounds. Over the past decade, electrochemical late-stage functionalization (eLSF) has gained major momentum, which is summarized herein up to February 2023.

Cancer-associated fibroblasts: Key players in shaping the tumor immune microenvironment.

Cancer immunotherapies have rapidly changed the therapeutic landscape for cancer. Nevertheless, most of the patients show innate or acquired resistance to these therapies. Studies conducted in recent years have highlighted an emerging role of cancer-associated fibroblasts (CAFs) in immune regulation that shapes the tumor immune microenvironment (TIME) and influences response to cancer immunotherapies. In this review, we outline recent advances in the understanding of phenotypic and functional heterogeneity of CAFs. We will focus on emerging roles of CAFs in shaping the TIME, especially under a framework of tumor immunity continuum, and discuss current and future CAF-targeting therapeutic strategies in particular in the context of optimizing the success of immunotherapies.

Iridium-Catalyzed Enantioselective Transfer Hydrogenation of 1,1-Dialkylethenes with Ethanol: Scope and Mechanism.

Despite half a century's advance in the field of transition-metal-catalyzed asymmetric alkene hydrogenation, the enantioselective hydrogenation of purely alkyl-substituted 1,1-dialkylethenes has remained an unmet challenge. Herein, we describe a chiral PCNOx-pincer iridium complex for asymmetric transfer hydrogenation of this alkene class with ethanol, furnishing all-alkyl-substituted tertiary stereocenters. High levels of enantioselectivity can be achieved in the reactions of substrates with secondary/primary and primary/primary alkyl combinations. The catalyst is further applied to the redox isomerization of disubstituted alkenols, producing a tertiary stereocenter remote to the resulting carbonyl group. Mechanistic studies reveal a dihydride species, (PCNOx)Ir(H)2, as the catalytically active intermediate, which can decay to a dimeric species (κ3-PCNOx)IrH(µ-H)2IrH(κ2-PCNOx) via a ligand-remetalation pathway. The catalyst deactivation under the hydrogenation conditions with H2 is much faster than that under the transfer hydrogenation conditions with EtOH, which explains why the (PCNOx)Ir catalyst is effective for the transfer hydrogenation but ineffective for the hydrogenation. The suppression of di-to-trisubstituted alkene isomerization by regioselective 1,2-insertion is partly responsible for the success of this system, underscoring the critical role played by the pincer ligand in enantioselective transfer hydrogenation of 1,1-dialkylethenes. Moreover, computational studies elucidate the significant influence of the London dispersion interaction between the ligand and the substrate on enantioselectivity control, as illustrated by the complete reversal of stereochemistry through cyclohexyl-to-cyclopropyl group substitution in the alkene substrates.

Atezolizumab plus bevacizumab versus active surveillance in patients with resected or ablated high-risk hepatocellular carcinoma (IMbrave050): a randomised, open-label, multicentre, phase 3 trial.

BACKGROUND: No adjuvant treatment has been established for patients who remain at high risk for hepatocellular carcinoma recurrence after curative-intent resection or ablation. We aimed to assess the efficacy of adjuvant atezolizumab plus bevacizumab versus active surveillance in patients with high-risk hepatocellular carcinoma. METHODS: In the global, open-label, phase 3 IMbrave050 study, adult patients with high-risk surgically resected or ablated hepatocellular carcinoma were recruited from 134 hospitals and medical centres in 26 countries in four WHO regions (European region, region of the Americas, South-East Asia region, and Western Pacific region). Patients were randomly assigned in a 1:1 ratio via an interactive voice-web response system using permuted blocks, using a block size of 4, to receive intravenous 1200 mg atezolizumab plus 15 mg/kg bevacizumab every 3 weeks for 17 cycles (12 months) or to active surveillance. The primary endpoint was recurrence-free survival by independent review facility assessment in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT04102098. FINDINGS: The intention-to-treat population included 668 patients randomly assigned between Dec 31, 2019, and Nov 25, 2021, to either atezolizumab plus bevacizumab (n=334) or to active surveillance (n=334). At the prespecified interim analysis (Oct 21, 2022), median duration of follow-up was 17·4 months (IQR 13·9-22·1). Adjuvant atezolizumab plus bevacizumab was associated with significantly improved recurrence-free survival (median, not evaluable [NE]; [95% CI 22·1-NE]) compared with active surveillance (median, NE [21·4-NE]; hazard ratio, 0·72 [adjusted 95% CI 0·53-0·98]; p=0·012). Grade 3 or 4 adverse events occurred in 136 (41%) of 332 patients who received atezolizumab plus bevacizumab and 44 (13%) of 330 patients in the active surveillance group. Grade 5 adverse events occurred in six patients (2%, two of which were treatment related) in the atezolizumab plus bevacizumab group, and one patient (<1%) in the active surveillance group. Both atezolizumab and bevacizumab were discontinued because of adverse events in 29 patients (9%) who received atezolizumab plus bevacizumab. INTERPRETATION: Among patients at high risk of hepatocellular carcinoma recurrence following curative-intent resection or ablation, recurrence-free survival was improved in those who received atezolizumab plus bevacizumab versus active surveillance. To our knowledge, IMbrave050 is the first phase 3 study of adjuvant treatment for hepatocellular carcinoma to report positive results. However, longer follow-up for both recurrence-free and overall survival is needed to assess the benefit-risk profile more fully. FUNDING: F Hoffmann-La Roche/Genentech.

Characterization of sub-nanosecond pulse compression based on frequency-detuning SBS.

High-frequency, high-power picosecond lasers have important and wide-ranging applications in laser ranging, optoelectronic countermeasures, and ultrafine industrial processing. Pulse compression based on stimulated Brillouin scattering (SBS) can achieve a highly efficient picosecond laser output, while improving the peak power and beam quality of the laser. In this paper, a generator-amplifier two-cell structure with frequency-detuning was proposed to achieve a pulse output that combines high compression ratio and high energy reflectivity. The experiment proved that under a pump pulse width of 15 ns and repetition frequency of 10 Hz, when the generator cell and amplifier cell media were selected as HT-230, the highest energy reflectivity of 46% and narrowest compression pulse width of 1.1 ns were achieved, and the pulse compression ratio was 13.6. When the amplifier cell was selected as FC-770 and the generator cell was selected as HT-230, an energy reflectivity of 52% and a compression pulse width of 840 ps could be achieved simultaneously, and the pulse compression ratio was 18.

High-power, gigahertz repetition frequency self-mode-locked Ho:GdVO4 laser resonantly pumped by a Tm-doped fiber laser.

A self-mode-locked Ho:GdVO4 laser with the GHz pulse repetition frequency oscillation near 2.06 µm was demonstrated for the first time to our knowledge. The output performances of the self-mode-locked Ho:GdVO4 laser were investigated for a few output coupler transmittances at the pulse repetition frequency of 1.89 GHz. At the incident pump power of 8.12 W, the maximum average output power was as high as 2.28 W, corresponding to the slope efficiency and optical-to-optical efficiency of 36.3% and 28.1%, respectively. This is the maximum average output for the 2 µm self-mode-locked solid-state laser with a GHz pulse repetition frequency. This work provides a new way for generating an efficient and a high-power ultrafast pulse laser with a GHz repetition frequency in the 2 µm wave band.

Self-healing propagation of a longitudinally varying vector optical beam for distance measurement.

Based on the longitudinal manipulation of polarization, a special vector optical beam (VOB) with customized polarization variation in propagation direction can be generated, whose properties and applications remain to be studied. Here, the self-healing propagation behaviors of the longitudinally varying VOB after an opaque object are investigated, and the localized polarization responses on the object distance are revealed. On this basis, characteristic parameters are defined to measure the distance of object, achieving a minimum relative error of 0.63% in a longitudinal range of 300 mm. Besides, the correlations and uncoupling methods of object distance and size are discussed. Our studies open new ways to use the structural properties of VOB and may be instructive for laser measurement.

High average output power, dual-wavelength synchronously self-mode-locked Ho:LLF laser operating at 2068.5 and 2069.2†nm.

A dual-wavelength synchronously self-mode-locked Ho:LLF laser operating at 2068.5 and 2069.2 nm was demonstrated. The maximum average output power was as high as 2.6 W with a pulse repetition frequency of 3.03 GHz. Meanwhile, the output power ratio of the dual-wavelength lasers can be effectively controlled by varying the incident pump power. To the best of our knowledge, this is the first dual-wavelength synchronously self-mode-locked Ho-doped fluoride solid state laser; moreover, our current experimental results represent the highest average output power from a GHz self-mode-locked oscillator in the 2 µm wave band.

HBCalculator: A Tool for Hydrogen Bond Distribution Calculations in Molecular Dynamics Simulations.

Hydrogen bonds, crucial noncovalent interactions in molecular systems, significantly impact biological, chemical, and energy-related processes; therefore, characterizing hydrogen bond information is of importance to fundamental studies. This work introduces the HBCalculator, a Tcl-based tool integrated with VMD for calculating 1D and 2D distributions of hydrogen bond density and strength. The tool facilitates spatial analysis, overcoming limitations in existing packages that lack direct spatial distribution output. By employing HBCalculator in MD simulations, three systems of cellulose/water and graphene/water interfaces, were tested to showcase its functionality. The 1D and 2D hydrogen bond distributions reveal insights into interfacial properties, reflecting the impact of material hydrophobicity. The simplicity of usage, along with its potential for diverse molecular systems, positions HBCalculator as a valuable tool for researchers exploring hydrogen bond networks.

TGFß attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells.

Therapeutic antibodies that block the programmed death-1 (PD-1)-programmed death-ligand 1 (PD-L1) pathway can induce robust and durable responses in patients with various cancers, including metastatic urothelial cancer. However, these responses only occur in a subset of patients. Elucidating the determinants of response and resistance is key to improving outcomes and developing new treatment strategies. Here we examined tumours from a large cohort of patients with metastatic urothelial cancer who were treated with an anti-PD-L1 agent (atezolizumab) and identified major determinants of clinical outcome. Response to treatment was associated with CD8+ T-effector cell phenotype and, to an even greater extent, high neoantigen or tumour mutation burden. Lack of response was associated with a signature of transforming growth factor ß (TGFß) signalling in fibroblasts. This occurred particularly in patients with tumours, which showed exclusion of CD8+ T cells from the tumour parenchyma that were instead found in the fibroblast- and collagen-rich peritumoural stroma; a common phenotype among patients with metastatic urothelial cancer. Using a mouse model that recapitulates this immune-excluded phenotype, we found that therapeutic co-administration of TGFß-blocking and anti-PD-L1 antibodies reduced TGFß signalling in stromal cells, facilitated T-cell penetration into the centre of tumours, and provoked vigorous anti-tumour immunity and tumour regression. Integration of these three independent biological features provides the best basis for understanding patient outcome in this setting and suggests that TGFß shapes the tumour microenvironment to restrain anti-tumour immunity by restricting T-cell infiltration.

Application of TiLOOP bra in implant-based breast reconstruction is associated with decreased complication risk compared with other meshes: A systematic review and meta-analysis.

BACKGROUND: TiLOOP bra has been used for over 15 years, however, evidence regarding its safety in implant-based breast reconstruction (IBBR) for patients with breast cancer after mastectomy is still limited. We performed this meta-analysis to evaluate its risks and benefits in IBBR comparing with other meshes. METHODS: Electronic databases were searched to identify relevant studies comparing postoperative complications between TiLOOP bra and other reconstruction techniques in IBBR with or without meshes. We also compared patient satisfaction in physical well-being between two groups. Risk ratios (RRs) and mean differences with 95% confidence interval (CI) were calculated. RESULTS: Seven studies representing 1203 cases were analyzed. Compared with other meshes, the use of TiLOOP bra significantly reduced the risk of infection (RR = 0.53, 95% CI, 0.32-0.86), seroma (RR = 0.21, 95% CI, 0.07-0.61), red breast syndrome (RR = 0.10, 95% CI, 0.02-0.45), and capsular contracture (RR = 0.20, 95% CI, 0.05-0.75). Patient satisfaction in physical well-being was comparable between two groups. CONCLUSIONS: TiLOOP bra in IBBR has a favored safety profile over other meshes, which significantly reduced postoperative complication risk and did not affect patient satisfaction. Although prospective well-designed controlled studies are still warranted, TiLOOP bra is safe and reliable at present.

Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma.

BACKGROUND: The combination of atezolizumab and bevacizumab showed encouraging antitumor activity and safety in a phase 1b trial involving patients with unresectable hepatocellular carcinoma. METHODS: In a global, open-label, phase 3 trial, patients with unresectable hepatocellular carcinoma who had not previously received systemic treatment were randomly assigned in a 2:1 ratio to receive either atezolizumab plus bevacizumab or sorafenib until unacceptable toxic effects occurred or there was a loss of clinical benefit. The coprimary end points were overall survival and progression-free survival in the intention-to-treat population, as assessed at an independent review facility according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1). RESULTS: The intention-to-treat population included 336 patients in the atezolizumab-bevacizumab group and 165 patients in the sorafenib group. At the time of the primary analysis (August 29, 2019), the hazard ratio for death with atezolizumab-bevacizumab as compared with sorafenib was 0.58 (95% confidence interval [CI], 0.42 to 0.79; P<0.001). Overall survival at 12 months was 67.2% (95% CI, 61.3 to 73.1) with atezolizumab-bevacizumab and 54.6% (95% CI, 45.2 to 64.0) with sorafenib. Median progression-free survival was 6.8 months (95% CI, 5.7 to 8.3) and 4.3 months (95% CI, 4.0 to 5.6) in the respective groups (hazard ratio for disease progression or death, 0.59; 95% CI, 0.47 to 0.76; P<0.001). Grade 3 or 4 adverse events occurred in 56.5% of 329 patients who received at least one dose of atezolizumab-bevacizumab and in 55.1% of 156 patients who received at least one dose of sorafenib. Grade 3 or 4 hypertension occurred in 15.2% of patients in the atezolizumab-bevacizumab group; however, other high-grade toxic effects were infrequent. CONCLUSIONS: In patients with unresectable hepatocellular carcinoma, atezolizumab combined with bevacizumab resulted in better overall and progression-free survival outcomes than sorafenib. (Funded by F. Hoffmann-La Roche/Genentech; ClinicalTrials.gov number, NCT03434379.).

A New Paradigm in Pincer Iridium Chemistry: PCN Complexes for (De)Hydrogenation Catalysis and Beyond.

The discovery and development of organometallic catalysts is of paramount importance in modern organic synthesis, among which the ligand scaffolds play a crucial role in controlling the activity and selectivity. Over the past several decades, d8 transition-metal complexes of pincer ligands have been developed extensively thanks to their easy structural modification, versatile reactivities, and high stability. One paradigm is the bis(phosphine)-based pincer iridium complexes PCP-Ir, which are highly active for alkane dehydrogenation, partly due to their high thermostability. However, except for alkane dehydrogenation and related transformations, few applications of pincer iridium catalysis have been seen in organic synthesis. This mainly arises from the low functional-group compatibility and poor substrate scope and the limited catalytic chemistry that invariably involves Ir(I/III) redox processes initiated by oxidative addition of substrates to 14-electron (PCP)Ir fragments (the proposed catalytically active intermediates). In this Account, we describe our endeavor on the development of a new family of PCN-Ir complexes with initial intention on creating more efficient alkane dehydrogenation catalysts. The replacement of a soft, σ-donor phosphine arm in the PCP ligands by a harder, π-acceptor N-heteroarene (pyridine or oxazoline) not only provides an additional platform to modify the structural properties but also offers new modes of bond activation and novel reactivities and catalysis. One uniqueness of the PCN-Ir system lies in the formation, via ortho-C(sp2)-H cyclometalation of the pyridine unit in the PCNPy ligand, of the neutral monohydride (PCC)IrIIIHL (L = neutral ligand), which catalyzes positional and stereoselective 1-alkene-to-(E)-2-alkene isomerization. Moreover, the PCN-Ir catalysts effect ethanol dehydrogenation without decarbonylation, allowing for transfer hydrogenation of unactivated alkenes and trans-selective semihydrogenation of internal alkynes with user-friendly ethanol as the H-donor. Another feature originates from the ability of the pentacoordinate hydrido chloride complex (PCN)IrIIIHCl to undergo reversible solvent-coordination-induced-ionization (SCII), furnishing a cationic monohydride [(PCN)IrIIIH(Sol)]+Cl- bearing an uncoordinated Cl anion that effects selective hydrometalation of internal alkynes over the corresponding (Z)-alkenes; the resulting (PCN)IrIII(vinyl)Cl complex undergoes amine-assisted formal alcoholysis involving the protonation of the Cl anion by the activated IrIII-bound EtOH, again via the SCII pathway. Together these elementary reactions lay the foundation for cis-selective semihydrogenation of alkynes with EtOH. Further, the design of the oxazoline-containing chiral complexes (PCNOxa)IrIIIHCl enables asymmetric transfer hydrogenation of alkenes/ketones with ethanol. The efficient catalytic α-alkylation of unactivated esters/amides with alcohols is another case showing the benefit that the PCN-Ir catalyst can offer. These examples illustrate the profound impact of the pincer ligands on the reactivities and catalysis. We hope this Account will provide an in-depth view into the fundamentals of pincer iridium chemistry and ultimately broaden its applications in organic synthesis.

High temporal waveform fidelity stimulated Brillouin scattering phase conjugate mirror using Novec-7500.

A high temporal waveform fidelity stimulated Brillouin scattering phase conjugate mirror (SBS-PCM) with high energy efficiency, based on a novel medium, Novec-7500, is proposed and practically achieved in this study. A theoretical analysis reveals that the temporal-domain waveform distortion is caused by the inherent pulse duration compression effect of the SBS, and this undesirable phenomenon can be significantly suppressed by decreasing the compression coefficient (CC afterwards), which is defined as the gain coefficient divided by the phonon lifetime, which coefficient and is identified as the key parameter for high waveform-fidelity in SBS-PCM. The feasibility of this approach was demonstrated experimentally, in which a reflected pulse with waveform symmetry equals to the pump and an average pulse duration of 0.974 τp (τp is the duration of pump) with an energy efficiency of over 90% was achieved using Novec-7500.

Modeling and characterization of high-power single frequency free-space Brillouin lasers.

Free-space Brillouin lasers (BLs) are capable of generating high-power, narrow-linewidth laser outputs at specific wavelengths. Although there have been impressive experimental demonstrations of these lasers, there is an absence of a corresponding theory that describes the dynamic processes that occur within them. This paper presents a time-independent analytical model that describes the generation of the first-order Stokes field within free-space BLs. This model is based on the cavity resonance enhancement theory and coupled wave equations that govern the processes of stimulated Brillouin scattering (SBS). This model is validated using an experimental diamond BL to numerically simulate the influence of the cavity design parameters on the SBS threshold, pump enhancement characteristics, and power of the generated Stokes field. Specifically, the model is used to determine the SBS cavity coupler reflectance to yield the maximum Stokes field output power and efficiency, which is also a function of the pump power and other cavity design parameters. This analysis shows that the appropriate choice of Brillouin cavity coupler reflectance maximizes the Stokes field output power for a given pump power. Furthermore, the onset of higher-order Stokes fields that are undesirable in the context of single-frequency laser operation were inhibited. This study aids in understanding the relationship between the cavity parameters and resultant laser characteristics for the design and optimization of laser systems.

Gain characteristics of stimulated Brillouin scattering in fused silica.

Stimulated Brillouin scattering (SBS) is a non-linear process which has the capacity to improve the beam quality and pulse characteristics of laser beams. In this paper, we theoretically and experimentally study the process of SBS in fused silica. In particular, we examine the energy reflection and pulse compression of input laser pulses as functions of focus position, pump energy and beam diameter. We utilized coupled wave equations and a distributed noise model to simulate the reflected energy and time waveform under different gain parameters. An experimental system is constructed and used to qualify the numerical simulations. The results reveal that the threshold for the SBS process and the energy reflectivity significantly change with laser focus position under the same pump and focusing parameters. Ultimately, the gain characteristics of the SBS material is the primary factor that influences the SBS output. This work presented here offers insight into the operation of short-length solid-state SBS lasers and serves as a basis for the design and optimization of such systems.

Influence of a longitudinal-mode on stimulated Brillouin scattering characteristics in fused silica.

Analyzing the longitudinal-mode of a pump can significantly prevent optical damage to solid media and expand the applications of solid media in high repetition rate stimulated Brillouin scattering (SBS). In this study, a Fabry-Pérot etalon was used to control the number of longitudinal-mode in a pump laser output. We studied the output characteristics of SBS in fused silica by considering both single- and multi-longitudinal-mode pumping. We analyzed and compared variations in the SBS threshold, energy reflectivity, linewidth, and waveform characteristics. The experimental results indicated that a pump operating in a single-longitudinal-mode had a 14% lower SBS threshold than one operating in a multi-longitudinal-mode. The proportion of the weak longitudinal-mode in the multi-longitudinal-mode was close to the threshold difference. The damage threshold of the multi-longitudinal-mode pumps was approximately 35 mJ (@12 ns, f = 300 mm). The Stokes linewidth and waveform exhibited opposite trends as the energy changed. Due to the time-bandwidth product, the linewidth and waveform tended to converge towards the pump. This study emphasizes the importance of using a single-longitudinal-mode pump in the development and use of solid-state SBS gain media.

Advanced Stretchable Photodetectors: Strategies, Materials and Devices.

Past decades have witnessed the generation of new stretchable photodetectors in electronic eyes, health sensing, wearable devices, intelligent monitoring and other fields. Stretchable devices require not only outstanding performance but also excellent flexibility, adaptability and stability. Innovative strategies have been proposed to realize the stretchability of devices. In addition, novel functional materials including zero-dimensional nanomaterials, one-dimensional inorganic nanomaterials, two-dimensional layered materials, organic materials, and organic-inorganic composite materials with excellent properties are emerging to continuously improve the performance of devices. Here, the recent research progress of stretchable photodetectors in terms of both various design methods and functional materials is outlined. The optical performance and stretchable properties are also comprehensively reviewed. Finally, a summary and the challenges associated with the application of stretchable photodetectors are presented.