Integration of social status and trust through interpersonal brain synchronization.

Trust can be a dynamic social process, during which the social identity of the interacting agents (e.g., an investor and a trustee) can bias trust outcomes. Here, we investigated how social status modulates trust and the neural mechanisms underlying this process. An investor and a trustee performed a 10-round repeated trust game while their brain activity was being simultaneously recorded using functional near-infrared spectroscopy. The social status (either high or low) of both investors and trustees was manipulated via a math competition task. The behavioral results showed that in the initial round, individuals invested more in low-status partners. However, the investment ratio increased faster as the number of rounds increased during trust interaction when individuals were paired with a high-status partner. This increasing trend was particularly prominent in the low (investor)-high (trustee) status group. Moreover, the low-high group showed increased investor-trustee brain synchronization in the right temporoparietal junction as the number of rounds increased, while brain activation in the right dorsolateral prefrontal cortex of the investor decreased as the number of rounds increased. Both interpersonal brain synchronization and brain activation predicted investment performance at the early stage; furthermore, two-brain data provided earlier predictions than did single-brain data. These effects were detectable in the investment phase in the low-high group only; no comparable effects were observed in the repayment phase or other groups. Overall, this study demonstrated a multi-brain mechanism for the integration of social status and trust.

Blockade of exosome generation by GW4869 inhibits the education of M2 macrophages in prostate cancer.

BACKGROUND: Tumor-associated macrophages are considered to be a major contributor affecting the development of tumors. Recently, numerous studies have shown that tumor cells were able to educate their microenvironment by delivering a significant amount of exosomes, however, the mechanism that exosomes from PCa cells work in macrophage polarization remains obscure. Therefore, we sought to determine whether blockade of exosome generation by GW4869, an inhibitor of exosome biogenesis, would impede macrophages from differentiating into M2 cells. RESULTS: In this study, we first obtained exosomes from the supernatant media of PCa cells cultured with exosome-free serum using the Magcapture™ Exosome Isolation Kit PS, and then investigated their effects on macrophages. Our data confirmed that exosomes released by prostate cancer cells can induce macrophages to differentiate into M2 cells. Mechanistically speaking, exosomes exert their effects on macrophages through activating the AKT and STAT3 signaling pathways. Importantly, treatment with GW4869 significantly inhibited the release of exosomes from PCa cells, and further impaired M2 differentiation of macrophages and their pro-tumor activity. We also demonstrated that GW4869 was able to inhibit the education of M2 macrophages, and then inhibit the progression of prostate cancer in vivo. CONCLUSIONS: In brief, our findings indicated that GW4869 impeded the PCa exosome-induced M2 differentiation of macrophages and the progression of prostate cancer, suggesting that GW4869 could play an important role in the treatment of prostate cancer metastasis as an inhibitor of tumor exosome secretion.

The averaged inter-brain coherence between the audience and a violinist predicts the popularity of violin performance.

Why is some music well-received whereas other music is not? Previous research has indicated the close temporal dependencies of neural activity among performers and among audiences. However, it is unknown whether similar neural contingencies exist between performers and audiences. Here, we used dual near-infrared spectroscopy (NIRS) to assess whether inter-brain synchronization between violinist and audience underlies the popularity of violin performance. In the experiment, individual audience members (16 females) watched pre-recorded videos, each lasting 100 â€‹s or so, in which a violinist performed 12 musical pieces. The results showed that the popularity of the performance correlated with the left-temporal inter-brain coherence (IBC) between the audience and the violinist. The correlation was stronger at late watching (>50 â€‹s) than at early watching (≤50 â€‹s). The smaller the Granger causality from the audience to the violinist was, the higher was the popularity of the piece with the audience. Discriminant analysis showed that the IBC could distinguish high popularity from low popularity. Further analysis using support vector regression showed that the IBC could also predict the popularity. These findings reveal the association of IBC with the popularity of violin performance. Music appreciation involves the brains of music producers and perceivers in a temporally aligned network through which audiences perceive the intentions of the performer and show positive emotions related to the musical performance.

Inhibition of let-7b-5p contributes to an anti-tumorigenic macrophage phenotype through the SOCS1/STAT pathway in prostate cancer.

BACKGROUND: Dysfunction of microRNAs (miRNAs) is a major cause of aberrant expression of inflammatory cytokines and contributes to macrophage polarization. Proinflammatory M1 macrophages promote T helper (Th) 1 responses and show tumoricidal activity, whereas M2 macrophages display regulatory functions in tissue repair and remodeling and promote Th2 immune responses. Previous studies have shown that miRNA let-7 is associated with cellular differentiation and that the expression of let-7b-5p is significantly augmented in M2 macrophages. However, the mechanism by which let-7b-5p regulates macrophage differentiation in prostate cancer (PCa) remains largely unknown. METHODS: Human macrophages were induced by blood monocytes from healthy male donors, and M1 macrophages were polarized by stimulating them overnight with 100 ng/ml of lipopolysaccharides and 100 ng/ml of IFN-γ. Conditioned medium from PC-3 cells was used to induce prostatic macrophages (M-CMs) in vitro, and we then transfected let-7b-5p mimics or inhibitors into M1 and M-CMs for 72 h. The expression of cluster of differentiation 206 (CD206) in each group was detected with the High-Throughput Connotation of Imaging System. We used quantitative real-time polymerase chain reaction (qRT-PCR) to examine the expression of the inflammatory cytokines IL-10, IL-12, IL-13, TNF-alpha, and let-7b in macrophages. SOCS1 protein levels were evaluated by ELISA, and the phosphorylation difference in STAT family member proteins was analyzed using CST signal-pathway chip. Phagocytosis by macrophages and the effect of macrophages on the proliferation of prostate cancer PC-3 cells were evaluated with phagocytosis assay or the Cell Counting Kit-8 (CCK-8) and colony formation assay. The relationship between SOCS1 and let-7b-5p was confirmed with a dual-luciferase reporter. RESULTS: The expression of cluster of differentiation 206 (CD206, a M2-like macrophage surface molecule) was significantly increased in M1 macrophages treated with let-7b-5p mimics, while CD206 expression was decreased in M-CMs treated with let-7b-5p inhibitors. Overexpression or knockdown of let-7b-5p significantly affected the expression of inflammatory factors in macrophages-including interleukin 10 (IL-10), IL-12, IL-13, and tumor necrosis factor alpha. Let-7b-5p downregulated the expression of suppressor of cytokine signaling 1 (SOCS1) and increased the phosphorylation of signal transducer and activator of transcription 1 (STAT1), STAT3, and STAT5a proteins in M-CMs and M1 macrophages with let-7b-5p mimics relative to the other groups. In addition, with the elevated expression of let-7b-5p, the phagocytosis by macrophages showed a commensurate and significant decrease. As a result, M-CMs treated with let-7b-5p inhibitors reduced the proliferation of PC-3 PCa cells. CONCLUSIONS: Collectively, these data indicated that let-7b-5p may regulate M2 polarization through the SOCS1/STAT pathway and that reversal of M2 differentiation by let-7b-5p inhibitors enhanced macrophage phagocytosis, ultimately inhibiting the proliferation of PCa cells.

[Effect of Crude Antigens from Ascaris lumbricoides on the Apoptosis and Secretion of IL-6 and TGF-ß of Human Lung Adenocarcinoma Cells].

OBJECTIVE: To investigate the effect of crude antigens of Ascaris lumbricoides on the secretion of IL-6 and TGF-ß of human lung adenocarcinoma cells (A549 cells), and the apoptosis of A549 cells. METHODS: Crude antigens of A. lumbricoides were prepared. A549 cells were co-cultured with 25, 125, and 500 µg/ml crude antigens of A. lumbricoides for 1, 18, and 24 h, named as low concentration group, medium concentration group, and high concentration group, respectively. Meanwhile, A549 cells were co-cultured with culture medium (negative control) and 12.5 µg/ml adriamycin (positive control). The apoptosis rate was detected by using Annexin V-FITC apoptosis detection kit. The cell changes were determined by flow cytometry. The levels of mRNA expression of IL-6 and TGF-ß were detected by ELISA and real time PCR, respectively. RESULTS: The apoptosis rate of A549 cells induced by crude antigens for 1, 18, and 24 h was significantly higher than that of negative control (P < 0.01). The apoptosis rate in medium concentration group (treated for 18 h) was highest [(47.10 ± 3.68)%]. After co-culture with 125 µg/ml crude antigens for 18 h, the proportion of G0/G1 phase cells increased and that of S phase cells decreased, and there was a significant difference between medium concentration group and negative control group. At the same time, the level of IL-6 increased with the increasing concentration of crude antigens. However, no significant difference was found in the level of TGF-ß among the groups. In the medium concentration group, mRNA expression levels of IL-6 (5.95 ± 0.31) and TGF-ß (3.43 ± 0.35) of A549 cells reached peak on the 18th hour, and were significantly higher than that of the control (P < 0.01). CONCLUSION: The cell cycle of A549 cells is blocked in G0/G1 phase induced by crude antigens of A. lumbricoides. And the apoptosis may be related to the changes in the level of TGF-ß and IL-6.

How self-disclosure of negative experiences shapes prosociality?

People frequently share their negative experiences and feelings with others. Little is known, however, about the social outcomes of sharing negative experiences and the underlying neural mechanisms. We addressed this dearth of knowledge by leveraging functional near-infrared spectroscopy (fNIRS) hyperscanning: while dyad participants took turns to share their own (self-disclosure group) or a stranger's (non-disclosure group) negative and neutral experiences, their respective brain activity was recorded simultaneously by fNIRS. We observed that sharing negative (relative to neutral) experiences enhanced greater mutual prosociality, emotional empathy and interpersonal neural synchronization (INS) at the left superior frontal cortex in the self-disclosure group compared to the non-disclosure group. Importantly, mediation analyses further revealed that in the self-disclosure (but not non-disclosure) group, the increased emotional empathy and INS elicited by sharing negative experiences relative to sharing neutral experiences promoted the enhanced prosociality through increasing interpersonal liking. These results indicate that self-disclosure of negative experiences can promote prosocial behaviors via social dynamics (defined as social affective and cognitive factors, including empathy and liking) and shared neural responses. Our findings suggest that when people express negative sentiments, they incline to follow up with positive actions.

Interpersonal Competition in Elderly Couples: A Functional Near-Infrared Spectroscopy Hyperscanning Study.

Elderly people tend not to compete with others, and if they do, the mechanism behind the competition is not clear. In this study, groups of elderly couples and matched cross-sex controls were recruited to perform a competitive button-pressing task, while their brain signals were simultaneously collected using functional near-infrared spectroscopy (fNIRS) hyperscanning. Several fundamental observations were made. First, controls showed attenuated interpersonal competition across task processes, but couples held the competition with each other. Second, couples demonstrated increased inter-brain synchronization (IBS) between the middle temporal cortex and the temporoparietal junction across task processes. Third, Granger causality analysis in couples revealed significant differences between the directions (i.e., from men to women, and from women to men) in the first half of the competitive task, whereas there was no significant difference in the second half. Finally, the groups of couples and controls could be successfully discriminated against based on IBS by using a machine-learning approach. In sum, these findings indicate that elderly couples can maintain interpersonal competition, and such maintenance might be associated with changes in the IBS of the mentalizing system. It suggests the possible positive impact of long-term spouse relationships on interpersonal interactions, both behaviorally and neurally, in terms of competition.

Ascaris: development of selected genotypes in mice.

Using nucleotide variation in the first internal transcribed spacer of nuclear ribosomal DNA, five different genotypes (designated G1-G5) have been identified and the preponderance of genotype G1 in humans and of genotype G3 in pigs led to the proposal that parasites bearing the two genotypes have an affinity for a particular host species. A subsequent study using eggs of genotype G1 from humans and G3 from pigs to infect pigs and mice indicated that there is a significant difference in the ability to infect and establish as larvae in mice and as adults in pigs between the two genotypes. Extending previous investigations, the present study investigated whether there are differences in development as designated by egg hatching, larvae migration and distribution in the mice between the Ascaris strains with known genotypes. Ascaris eggs of genotypes G1 (predominating in human-derived worms) and G3 (predominating in pig-derived worms) were used to infect C57BL/6 mice orally. Eggs/larvae were examined from the small and large intestines, thoracic and abdominal cavities, peripheral blood, livers and lungs at intervals of 2h until 12h post-infection, then periodically until 34 days of infection. Results showed distinct differences in egg hatching (the timing and location of hatching, and the numbers hatched), and in larvae migration and distribution (the means and constituent ratios, the time of peak recovery, and larvae reappearing in intestines) between the two strains. The results can explain the findings of significantly higher larval recovery of genotype G1 than G3 in the mice, and may shed some enlightenment to understand the difference in host affiliation of Ascaris of different genotypes.

Functional Connectivity Signatures Underlying Simultaneous Language Translation in Interpreters and Non-Interpreters of Mandarin and English: An fNIRS Study.

Recent neuroimaging research has suggested that interpreters and non-interpreters elicit different brain activation patterns during simultaneous language translation. However, whether these two groups have different functional connectivity during such a task, and how the neural coupling is among brain subregions, are still not well understood. In this study, we recruited Mandarin (L1)/English (L2) interpreters and non-interpreter bilinguals, whom we asked to perform simultaneous language translation and reading tasks. Functional near-infrared spectroscopy (fNIRS) was used to collect cortical brain data for participants during each task, using 68 channels that covered the prefrontal cortex and the bilateral perisylvian regions. Our findings revealed both interpreter and non-interpreter groups recruited the right dorsolateral prefrontal hub when completing the simultaneous language translation tasks. We also found different functional connectivity between the groups. The interpreter group was characterized by information exchange between the frontal cortex and Wernicke's area. In comparison, the non-interpreter group revealed neural coupling between the frontal cortex and Broca's area. These findings indicate expertise modulates functional connectivity, possibly because of more developed cognitive skills associated with executive functions in interpreters.

Distinct neural couplings to shared goal and action coordination in joint action: evidence based on fNIRS hyperscanning.

Joint action is central to human nature, enabling individuals to coordinate in time and space to achieve a joint outcome. Such interaction typically involves two key elements: shared goal and action coordination. Yet, the substrates entrained to these two components in joint action remained unclear. In the current study, dyads performed two tasks involving both sharing goal and action coordination, i.e. complementary joint action and imitative joint action, a task only involving shared goal and a task only involving action coordination, while their brain activities were recorded by the functional near-infrared spectroscopy hyperscanning technique. The results showed that both complementary and imitative joint action (i.e. involving shared goal and action coordination) elicited better behavioral performance than the task only involving shared goal/action coordination. We observed that the interbrain synchronization (IBS) at the right inferior frontal cortex (IFC) entrained more to shared goal, while left-IFC IBS entrained more to action coordination. We also observed that the right-IFC IBS was greater during completing a complementary action than an imitative action. Our results suggest that IFC plays an important role in joint action, with distinct lateralization for the sub-components of joint action.

The intrapersonal and interpersonal consequences of interpersonal synchrony.

Interpersonal synchrony, the time-matching behaviors, is pervasive in human interactions. This resonation of movements or other forms was generally considered as one of critical survival skills for humans, as the important consequences of synchronizing with other persons in review of the empirical data in this article. These include positive affects towards and between interacting partners, but also include complex effects on the individual level. The intrapersonal effects of interpersonal synchrony are varied with positive or negative ones, including cognitive style, attitude bias, mood state, self-regulatory ability, and academic performance. At the interpersonal level, synchronized movement consistently affects the interaction with the partner and his/her affiliations, but they can be eliminated or magnified by several moderators, such as physiological arousal, shared intentionality, group bias, and musical rhythm. Finally, the research discussed the possible mechanisms underlying the effects of interpersonal synchrony in psychological and biological aspects.

Human creativity escapes in the struggle against threat: Evidence from neural mechanisms.

The damaging effect of threat on creativity has been confirmed by many studies. However, the neural mechanism underlying this effect has not been clarified. We designed an experiment to explore changes in brain activation when creativity is threatened. Specifically, participants performed the Chinese Remote Associates Test (RAT) under three conditions. The control condition was accompanied by no sound, the neutral condition was accompanied by unpredictable neutral sounds, and the threat condition was manipulated through unpredictable aversive sounds. We used functional near-infrared spectroscopy measurements to collect cognitive neurological data. The results showed that the threat condition reduced the accuracy and response time of the RAT and led to individual negative emotions. Participants' prefrontal cortex and supramarginal gyrus activation decreased under threat. These results provide a reference for clarifying the negative impact of threat on creativity and highlight its cognitive neural mechanisms.

Musical Meter Induces Interbrain Synchronization during Interpersonal Coordination.

Music induces people to coordinate with one another. Here, we conduct two experiments to examine the underlying mechanism of the interbrain synchronization (IBS) that is induced by interpersonal coordination when people are exposed to musical beat and meter. In experiment 1, brain signals at the frontal cortex were recorded simultaneously from two participants of a dyad by using functional near-infrared spectroscopy (fNIRS) hyperscanning, while each tapped their fingers to aural feedback from their partner (coordination task) or from themselves (independence task) with and without the musical meter. The results showed enhanced IBS at the left-middle frontal cortex in case of the coordination task with musical beat and meter. The IBS was significantly correlated with the participants performance in terms of coordination. In experiment 2, we further examined the IBS while the participants coordinated their behaviors in various metrical contexts, such as strong and weak meters (i.e., high/low loudness of acoustically accenting beats). The results showed that strong meters elicited higher IBS at the middle frontal cortex than weak meters. These findings reveal that the musical beat and meter can affect brain-to-brain coupling in action coordination between people, and provide insights into the interbrain mechanism underlying the effects of music on cooperation.

Optical Mapping of Brain Activity Underlying Directionality and Its Modulation by Expertise in Mandarin/English Interpreting.

Recent neuroimaging research has suggested that unequal cognitive efforts exist between interpreting from language 1 (L1) to language 2 (L2) compared with interpreting from L2 to L1. However, the neural substrates that underlie this directionality effect are not yet well understood. Whether directionality is modulated by interpreting expertise also remains unknown. In this study, we recruited two groups of Mandarin (L1)/English (L2) bilingual speakers with varying levels of interpreting expertise and asked them to perform interpreting and reading tasks. Functional near-infrared spectroscopy (fNIRS) was used to collect cortical brain data for participants during each task, using 68 channels that covered the prefrontal cortex and the bilateral perisylvian regions. The interpreting-related neuroimaging data was normalized by using both L1 and L2 reading tasks, to control the function of reading and vocalization respectively. Our findings revealed the directionality effect in both groups, with forward interpreting (from L1 to L2) produced more pronounced brain activity, when normalized for reading. We also found that directionality was modulated by interpreting expertise in both normalizations. For the group with relatively high expertise, the activated brain regions included the right Broca's area and the left premotor and supplementary motor cortex; whereas for the group with relatively low expertise, the activated brain areas covered the superior temporal gyrus, the dorsolateral prefrontal cortex (DLPFC), the Broca's area, and visual area 3 in the right hemisphere. These findings indicated that interpreting expertise modulated brain activation, possibly because of more developed cognitive skills associated with executive functions in experienced interpreters.

How to Calculate and Validate Inter-brain Synchronization in a fNIRS Hyperscanning Study.

The dynamics between coupled brains of individuals have been increasingly represented by inter-brain synchronization (IBS) when they coordinate with each other, mostly using simultaneous-recording signals of brains (namely hyperscanning) with fNIRS. In fNIRS hyperscanning studies, IBS has been commonly assessed through the wavelet transform coherence (WTC) method because of its advantage on expanding time series into time-frequency space where oscillations can be seen in a highly intuitive way. The observed IBS can be further validated via the permutation-based random pairing of the trial, partner, and condition. Here, a protocol is presented to describe how to obtain brain signals via fNIRS technology, calculate IBS through the WTC method, and validate IBS by permutation in a hyperscanning study. Further, we discuss the critical issues when using the above methods, including the choice of fNIRS signals, methods of data preprocessing, and optional parameters of computations. In summary, using the WTC method and permutation is a potentially standard pipeline for analyzing IBS in fNIRS hyperscanning studies, contributing to both the reproducibility and reliability of IBS.

Gene silencing of indoleamine 2,3-dioxygenase 1 inhibits lung cancer growth by suppressing T-cell exhaustion.

Indoleamine 2,3-dioxygenase 1 (IDO1), which degrades the essential amino acid tryptophan, exerts immunosuppressive functions and serves a crucial role in multiple types tumor progression, including non-small-cell lung cancer (NSCLC) and melanoma. Recent studies have reported that T-cell exhaustion is increased during tumor progression, which impairs the antitumor immune response. However, the association between IDO1 and T-cell exhaustion during tumor progression remains unknown. The present study evaluated the effect of IDO1 on T-cell exhaustion in lung cancer mice. The present study demonstrated that IDO1 knockdown by small interfering RNA in the LLC cell line inhibited T-cell exhaustion. Furthermore, the role of IDO1 in T-cell exhaustion during lung cancer progression was determined in an in vivo mouse model using IDO1 short hairpin RNA (shRNA). The results demonstrated that inhibition of IDO1 activity by shRNA administration in vivo significantly delayed the onset and growth of tumors. In addition, the expression levels of the inhibitory receptors programmed death-1 (PD-1) and B and T lymphocyte attenuator (BTLA) were increased in T-cells from the lung tumor-bearing mice, whereas interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-α) levels in serum were decreased compared with the control mice. However, no difference in the absolute number of T cells was observed, including CD4+ and CD8+ T cells. In addition, IDO1 knockdown by shRNA inhibited T-cell exhaustion in lung tumor-bearing mice, which was characterized by decreased expression of PD-1 and BTLA on T cells. By contrast, IL-2 and TNF-α levels in serum were increased in IDO1-shRNA-treated mice. By using a shRNA approach, the present study demonstrated that IDO1 activity may be involved in tumor growth, and that IDO1 silencing may inhibit tumor progression by impeding the process of T-cell exhaustion.

Coordination Elicits Synchronous Brain Activity Between Co-actors: Frequency Ratio Matters.

People could behave in two different ways when engaging in interpersonal coordination activities: moving at the same frequency (isofrequency pattern, IP; the movement frequency ratio is 1:1) or at different frequencies (multifrequency pattern, MP; the movement frequency ratio is non 1:1). However, how the interpersonal coordination pattern modulates coordination outcome and the related brain-to-brain connectivity is not fully understood. Here, we adopted a continuous joint drawing task in which two participants co-drew parallelogram shapes according to two coordination patterns (i.e., IP vs. MP) while their brain activities were simultaneously recorded by the functional near-infrared spectroscopy (fNIRS) based hyperscanning technique. Dyads showed better coordination performance, as well as relatively greater interpersonal brain synchronization (IBS) at the left frontopolar area, in the MP condition compared to the IP condition. Granger causality analyses further disclosed the bidirectional influences between the brains of the coordinating individuals. Such interpersonal influences were enhanced when individuals coordinated in the MP condition. Finally, the IBS during coordination was related to the dyadic self-control level. Taken together, our study revealed that interpersonal multifrequency coordination pattern facilitates the coordination efficiency, which was associated with the enhanced brain-to-brain connectivity. Our work also suggests the potentially positive role of self-control during the interpersonal coordination process.

Brain-to-brain synchronization across two persons predicts mutual prosociality.

People tend to be more prosocial after synchronizing behaviors with others, yet the underlying neural mechanisms are rarely known. In this study, participant dyads performed either a coordination task or an independence task, with their brain activations recorded via the functional near-infrared spectroscopy hyperscanning technique. Participant dyads in the coordination group showed higher synchronized behaviors and greater subsequent inclination to help each other than those in the independence group, indicating the prosocial effect of interpersonal synchrony. Importantly, the coordination group demonstrated the significant task-related brain coherence, namely the interbrain synchronization, at the left middle frontal area. The detected interbrain synchronization was sensitive to shared intentionality between participants and was correlated with the mutual prosocial inclination. Further, the task-related brain coherence played a mediation role in the prosocial effect of interpersonal synchrony. This study reveals the relevance of brain-to-brain synchronization among individuals with subsequent mutual prosocial inclination and suggests the neural mechanism associating with shared cognition for the facilitation of interpersonal synchrony on prosociality.

Gene silencing of indoleamine 2,3-dioxygenase hinders tumor growth through angiogenesis inhibition.

The significance of indoleamine 2,3-dioxygenase-1 (IDO1) has been studied in various types of tumors, but the relationship between IDO1 and tumor angiogenesis needs further delineation. We aimed to clarify the relationship between tumor angiogenesis and IDO1 expression, and to explore the possibility of IDO1-targeting molecular therapy for lung cancer. For the first time, we found that silencing the IDO1 gene using small interfering RNA (siRNA) inhibits in vitro cancer cell invasion and migration. We further demonstrated that knockdown of IDO1 decreased the formation of vasculogenic mimicry. In addition to these in vitro findings, we also demonstrated that in vivo IDO1 gene silencing using short hairpin RNA (shRNA) delayed tumor onset and inhibited tumor growth in the mouse model. Immunostaining showed that IDO1 gene silencing inhibited tumor angiogenesis. Moreover, the expression of IDO1 was associated with microvessel density (MVD) labeled by CD34 and CD146. These findings indicate that IDO1 has the potential to participate in or contribute to the formation of new capillaries, supporting the applicability of IDO1-targeting molecular therapy in lung cancer.