Exploring treatment options in cancer: Tumor treatment strategies.

Traditional therapeutic approaches such as chemotherapy and radiation therapy have burdened cancer patients with onerous physical and psychological challenges. Encouragingly, the landscape of tumor treatment has undergone a comprehensive and remarkable transformation. Emerging as fervently pursued modalities are small molecule targeted agents, antibody-drug conjugates (ADCs), cell-based therapies, and gene therapy. These cutting-edge treatment modalities not only afford personalized and precise tumor targeting, but also provide patients with enhanced therapeutic comfort and the potential to impede disease progression. Nonetheless, it is acknowledged that these therapeutic strategies still harbour untapped potential for further advancement. Gaining a comprehensive understanding of the merits and limitations of these treatment modalities holds the promise of offering novel perspectives for clinical practice and foundational research endeavours. In this review, we discussed the different treatment modalities, including small molecule targeted drugs, peptide drugs, antibody drugs, cell therapy, and gene therapy. It will provide a detailed explanation of each method, addressing their status of development, clinical challenges, and potential solutions. The aim is to assist clinicians and researchers in gaining a deeper understanding of these diverse treatment options, enabling them to carry out effective treatment and advance their research more efficiently.

Synchronous papillary and follicular thyroid carcinomas: the first retrospective cohort study and literature review.

Background: Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) contribute to more than 95% of thyroid malignancies. However, synchronous PTC and FTC are less common; it is most commonly discovered incidentally as synchronous malignancies during operation, which adds difficulties to intraoperative decision-making and postoperative treatment. Therefore, we analyzed the clinicopathological characteristics and prognosis of patients with PTC and FTC in our center. Methods: We conducted a search of single PTC, single FTC, and synchronous PTC/FTC patients who received initial surgery treatment at Fudan University Shanghai Cancer Center from 2006 to 2018 and collected paraffin-embedded samples of synchronous patients. Clinicopathological characteristics were collected from the electronic medical record system. Follow-up was performed through telephone contact or medical records. Exome sequencing was performed by ThyroLead panel. Results: Total of 42 synchronous PTC/FTC patients, 244 single FTC patients, and 2,959 single PTC patients were included. It showed a similarity between the clinicopathological features of synchronous thyroid cancer patients and single PTC patients, with a greater proportion of females, higher probabilities of lymph node metastasis, and higher rate of concurrence of Hashimoto's disease. The disease-free survival (DFS) curve indicated a worse prognosis of the synchronous group and single PTC group compared to the single FTC group, who had a propensity for neck lymph node recurrence; however, logistic multivariate regression analysis did not find any factor related to recurrence in the synchronous group. After re-checking pathology, DNA extraction, and quality control, genetic alteration information of 62 samples including primary tumors and metastatic lymph nodes from 35 synchronous cancer patients was displayed. In total, 81 mutations and 1 fusion gene were identified, including mutations related to outcomes and targeted therapy. Besides, some rare mutations in thyroid cancer were found in these patients. Conclusions: To conclude, synchronous PTC/FTC tend to be incidentally discovered during or after operation, behaving more like single PTC. The prognosis of synchronous patients is worse than that of single FTC patients and supplemental cervical lymph node dissection, total thyroidectomy, and postoperative radioiodine therapy should be taken into consideration after diagnosis. The next-generation sequencing (NGS) showed a unique molecular feature of synchronous patients with some rare mutations.

A distinct tumor microenvironment makes anaplastic thyroid cancer more lethal but immunotherapy sensitive than papillary thyroid cancer.

Both anaplastic thyroid cancer (ATC) and papillary thyroid cancer (PTC) originate from thyroid follicular epithelial cells, but ATC has a significantly worse prognosis and shows resistance to conventional therapies. However, clinical trials found that immunotherapy works better in ATC than late-stage PTC. Here, we used single-cell RNA sequencing (scRNA-Seq) to generate a single-cell atlas of thyroid cancer. Differences in ATC and PTC tumor microenvironment components (including malignant cells, stromal cells, and immune cells) leading to the polarized prognoses were identified. Intriguingly, we found that CXCL13+ T lymphocytes were enriched in ATC samples and might promote the development of early tertiary lymphoid structure (TLS). Last, murine experiments and scRNA-Seq analysis of a treated patient's tumor demonstrated that famitinib plus anti-PD-1 antibody could advance TLS in thyroid cancer. We displayed the cellular landscape of ATC and PTC, finding that CXCL13+ T cells and early TLS might make ATC more sensitive to immunotherapy.

Amine-releasable Mediator In situ Repair Perovskites for Efficient and Stable Perovskite Solar Cells.

Residual lead iodide (PbI2) is deemed to a double-edged sword in perovskite film as small amounts of PbI2 are beneficial to the photovoltaic performance, but excessive will cause degradation of photovoltaic performance and stability. Herein, an in situ repair strategy has been developed by introducing amine-releasable mediator (methylammonium pyridine-2-carboxylic, MAPyA) to eliminate over-residual PbI2 and regulate the crystal quality of perovskite film. Notably, MAPyA can be partially decomposed into methylamine (MA) gas and pyridine-2-carboxylic (PyA) during high temperature annealing. The released MA can locally form liquid intermediate phase, facilitating the reconstruction of perovskite microcrystals and residual PbI2. Moreover, the leftover PyA is confirmed to effectively passivate the uncoordinated lead ions in final perovskite film. Based upon this, superior perovskite film with optimized crystal structure and holistic negligible PbI2 is acquired. The assembled device realizes outstanding efficiency of 24.06 %, and exhibits a remarkable operational stability that maintaining 87 % of its origin efficiency after continuous illumination for 1480 h. And the unencapsulated MAPyA-treated devices present significant uplift in humidity stability (maintaining ~93 % of the initial efficiency over 1500 h, 50-60 % relative humidity). Furthermore, the further optimization of this strategy with nanoimprint technology proves its superiority in the amplificative preparation for perovskite films.

Achieving Desired Pseudo-Planar Heterojunction Organic Solar Cells via Binary-Dilution Strategy.

The sequential deposition process has demonstrated the great possibility to achieve a photolayer architecture with an ideal gradient phase separation morphology, which has a vital influence on the physical processes that determine the performance of organic solar cells (OSCs). However, the controllable preparation of pseudo-planar heterojunction (P-PHJ) with gradient distribution has not been effectively elucidated. Herein, a binary-dilution strategy is proposed, the PM6 solution with micro acceptor BO-4Cl and the L8-BO solution with micro donor PM6 respectively, to form P-PHJ film. This architecture exists good donor (D) and acceptor (A) vertical gradient distribution and larger D/A interpenetrating regions, which promotes exciton generation and dissociation, shortens charge transport distance and optimizes carrier dynamics. Moreover, the dilution of PM6 by BO-4Cl promotes the regulation of active layer aggregation size and phase purity, thus alleviating energy disorder and voltage loss. As a result, the P-PHJ device exhibits an outstanding power conversion efficiency of 19.32% with an excellent short-circuit current density of 26.92 mA cm-2 , much higher than planar binary heterojunction (17.67%) and ternary bulk heterojunction (18.49%) devices. This research proves a simple but effective method to provide an avenue for constructing desirable active layer morphology and high-performance OSCs.

Synchronous Elimination of Excess Photoinstable PbI2 and Interfacial Band Mismatch for Efficient and Stable Perovskite Solar Cells.

Eliminating the undesired photoinstability of excess lead iodide (PbI2 ) in the perovskite film and reducing the energy mismatch between the perovskite layer and heterogeneous interfaces are urgent issues to be addressed in the preparation of perovskite solar cells (PVSCs) by two-step sequential deposition method. Here, the 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIMBF4 ) is employed to convert superfluous PbI2 to more robust 1D EMIMPbI3 which can withstand lattice strain, while forming an interfacial dipole layer at the SnO2 /perovskite interface to reconfigure the interfacial energy band structure and accelerate the charge extraction. Consequently, the unencapsulated PVSCs device attains a champion efficiency of 24.28 % with one of the highest open-circuit voltage (1.19 V). Moreover, the unencapsulated devices showcase significantly improved thermal stability, enhanced environmental stability and remarkable operational stability accompanied by 85 % of primitive efficiency retained over 1500 h at maximum power point tracking under continuous illumination.

Targeting MFGE8 secreted by cancer-associated fibroblasts blocks angiogenesis and metastasis in esophageal squamous cell carcinoma.

Cancer-associated fibroblasts (CAFs) play vital roles in establishing a suitable tumor microenvironment. In this study, RNA sequencing data revealed that CAFs could promote cell proliferation, angiogenesis, and ECM reconstitution by binding to integrin families and activating PI3K/AKT pathways in esophageal squamous cell carcinoma (ESCC). The secretions of CAFs play an important role in regulating these biological activities. Among these secretions, we found that MFGE8 is specifically secreted by CAFs in ESCC. Additionally, the secreted MFGE8 protein is essential in CAF-regulated vascularization, tumor proliferation, drug resistance, and metastasis. By binding to Integrin αVß3/αVß5 receptors, MFGE8 promotes tumor progression by activating both the PI3K/AKT and ERK/AKT pathways. Interestingly, the biological function of MFGE8 secreted by CAFs fully demonstrated the major role of CAFs in ESCC and its mode of mechanism, showing that MFGE8 could be a driver factor of CAFs in remodeling the tumor environment. In vivo treatment targeting CAFs-secreting MFGE8 or its receptor produced significant inhibitory effects on ESCC growth and metastasis, which provides an approach for the treatment of ESCC.

TERT accelerates BRAF mutant-induced thyroid cancer dedifferentiation and progression by regulating ribosome biogenesis.

TERT reactivation occurs frequently in human malignancies, especially advanced cancers. However, in vivo functions of TERT reactivation in cancer progression and the underlying mechanism are not fully understood. In this study, we expressed TERT and/or active BRAF (BRAF V600E) specifically in mouse thyroid epithelium. While BRAF V600E alone induced papillary thyroid cancer (PTC), coexpression of BRAF V600E and TERT resulted in poorly differentiated thyroid carcinoma (PDTC). Spatial transcriptome analysis revealed that tumors from mice coexpressing BRAF V600E and TERT were highly heterogeneous, and cell dedifferentiation was positively correlated with ribosomal biogenesis. Mechanistically, TERT boosted ribosomal RNA (rRNA) expression and protein synthesis by interacting with multiple proteins involved in ribosomal biogenesis. Furthermore, we found that CX-5461, an rRNA transcription inhibitor, effectively blocked proliferation and induced redifferentiation of thyroid cancer. Thus, TERT promotes thyroid cancer progression by inducing cancer cell dedifferentiation, and ribosome inhibition represents a potential strategy to treat TERT-reactivated cancers.

Monodisperse Adducts-Induced Homogeneous Nucleation Towards High-Quality Tin-Based Perovskite Film.

The classic solvent system can't sufficiently separate one-dimensional edge-sharing SnI2 crystals in solution, which severely restricts the fabrication of high-quality tin-based perovskite film. Herein, a strong Lewis base (hexamethylphosphoramide, HMPA) has been introduced to coordinate Sn2+ to modulate solvation behaviours on perovskite precursor and regulate crystallization kinetics. The large molecular volume of HMPA and stronger bind energy of SnI2 ⋅ 2HMPA (-0.595 eV vs -0.118 eV for SnI2 ⋅ 2DMSO) change the solvation structure of SnI2 from edge-sharing cluster to monodisperse adduct, which contributes to uniform nucleation sites and prolongs crystal growth process. Delightfully, a fully-covered perovskite film is formed on the large-area substrate and tin-based perovskite solar cells processed with HMPA exhibit an excellent efficiency of 13.46 %. This research provides novel insights and directions for the solution preparation of smooth and uniform large-area tin-based perovskite film.

Inhibition of Ion Migration for Highly Efficient and Stable Perovskite Solar Cells.

In recent years, organic-inorganic halide perovskites are now emerging as the most attractive alternatives for next-generation photovoltaic devices, due to their excellent optoelectronic characteristics and low manufacturing cost. However, the resultant perovskite solar cells (PVSCs) are intrinsically unstable owing to ion migration, which severely impedes performance enhancement, even with device encapsulation. There is no doubt that the investigation of ion migration and the summarization of recent advances in inhibition strategies are necessary to develop "state-of-the-art" PVSCs with high intrinsic stability for accelerated commercialization. This review systematically elaborates on the generation and fundamental mechanisms of ion migration in PVSCs, the impact of ion migration on hysteresis, phase segregation, and operational stability, and the characterizations for ion migration in PVSCs. Then, many related works on the strategies for inhibiting ion migration toward highly efficient and stable PVSCs are summarized. Finally, the perspectives on the current obstacles and prospective strategies for inhibition of ion migration in PVSCs to boost operational stability and meet all of the requirements for commercialization success are summarized.

Multifunctional Metal-Organic Frameworks Capsules Modulate Reactivity of Lead Iodide toward Efficient Perovskite Solar Cells with UV Resistance.

The two-step sequential deposition process is demonstrated as a reliable technology for the fabrication of efficient perovskite solar cells (PVSCs). However, the complete conversion of dense PbI2 to perovskite in planar PVSCs is tough without mesoporous titanium dioxide as support. Herein, multifunctional capsules consisting of zeolitic imidazolate framework-8 (ZIF-8) encapsulant and formamidinium iodide (FAI) are introduced between tin oxide (SnO2 ) and lead iodide (PbI2 ) layer. Intriguingly, the capsule dopant interlayer benefits the formation of porous PbI2 film due to the porous nanostructure of ZIF-8 that is favorable for the subsequent intercalation reaction. Furthermore, the constituent of the perovskite precursor in ZIF-8 pores can convert into the crystal nuclei of perovskite by reacting with PbI2 first, thereby promoting further perovskite crystallization. Significantly, the incorporation of ZIF-8 can enhance the resistance of perovskite against UV illumination due to down-conversion effect. Consequently, the modified device achieves a champion power conversion efficiency (PCE) of 24.08% and displays enhanced UV stability, which can sustain 83% of its original PCE under 365 nm UV illumination for 300 h. Moreover, the unencapsulated device maintains 90% of initial PCE after 1500 h storage in dark ambient conditions with a relative humidity range of 50%-70%.

Cancer stem cells: Recent insights and therapies.

Tumors are intricate ecosystems containing malignant components that generate adaptive and evolutionarily driven abnormal tissues. Through self-renewal and differentiation, cancers are reconstructed by a dynamic subset of stem-like cells that enforce tumor heterogeneity and remodel the tumor microenvironment (TME). Through recent technology advances, we are now better equipped to investigate the fundamental role of cancer stem cells (CSCs) in cancer biology. In this review, we discuss the latest insights into characteristics, markers and mechanism of CSCs and describe the crosstalk between CSCs and other cells in TME. Additionally, we explore the performance of single-cell sequencing and spatial transcriptome analysis in CSCs studies and summarize the therapeutic strategies to eliminate CSCs, which could broaden the understanding of CSCs and exploit for therapeutic benefit.

Development and validation of a gene model predicting lymph node metastasis and prognosis of oral squamous cell carcinoma based on single-cell and bulk RNA-seq analysis.

BACKGROUND: Lymph node metastasis can independently predict oral squamous cell carcinoma patients' survival. This study would investigate the genetic and cellular differences between oral squamous cell carcinoma with positive and negative lymph node metastases. METHODS: We gathered single-cell RNA sequencing and bulk gene expression data from the Cancer Genome Atlas and Gene Expression Omnibus databases. Sixty lymph node-metastasis-related genes were discovered with refined single-cell RNA sequencing data analysis, and consensus clustering provided three molecular subtypes of oral squamous cell carcinoma. Least absolute shrinkage and selection operator analyses were then utilized to establish a five-gene risk model. CIBERSORT analysis revealed the immune infiltration profile of different risk subgroups. RESULTS: Oral squamous cell carcinoma patients were classified into three subtypes based on the 60 lymph node-metastasis-related key genes identified by single-cell RNA sequencing data. Patients in Subtype 3 showed a tendency for lymph node metastasis and poorer prognosis. Moreover, five biomarkers were selected from the 60 genes to construct a five-gene risk model evaluating the risk of lymph node metastasis. A lower probability of lymph node metastasis and a better prognosis was observed in the low-risk group. The immune infiltration of three different risk groups was explored with CIBERSORT. Besides, further analysis implied different sensitivities of anticancer drugs, including immunotherapy drugs and targeted compounds, in the three risk groups. CONCLUSION: In view of intratumoral heterogeneity, we found 60 genes associated with lymph node metastasis of oral squamous cell carcinoma. Subsequently, we constructed a five-gene signature that could improve the prediction of lymph node metastasis, clinical outcome, and promote individualized treatment strategies for oral squamous cell carcinoma.

Multidentate Chelation Heals Structural Imperfections for Minimized Recombination Loss in Lead-Free Perovskite Solar Cells.

Tin-based perovskite solar cells (Sn-PSCs) have emerged as promising environmentally viable photovoltaic technologies, but still suffer from severe non-radiative recombination loss due to the presence of abundant deep-level defects in the perovskite film and under-optimized carrier dynamics throughout the device. Herein, we healed the structural imperfections of Sn perovskites in an "inside-out" manner by incorporating a new class of biocompatible chelating agent with multidentate claws, namely, 2-Guanidinoacetic acid (GAA), which passivated a variety of deep-level Sn-related and I-related defects, cooperatively reinforced the passivation efficacy, released the lattice strain, improved the structural toughness, and promoted the carrier transport of Sn perovskites. Encouragingly, an efficiency of 13.7 % with a small voltage deficit of ≈0.47 V has been achieved for the GAA-modified Sn-PSCs. GAA modification also extended the lifespan of Sn-PSCs over 1200 hours.

Pseudo-Planar Heterojunction Organic Photovoltaics with Optimized Light Utilization for Printable Solar Windows.

The existing conformation of the active layer is defective for employment of semitransparent organic solar cells (ST-OSCs) in solar windows. Herein, scalable solar windows are successfully printed by introducing a pseudo-planar heterojunction (PPHJ) structure. The PPHJ structure can effectively improve the average visible transmittance (AVT) value while boosting the power conversion efficiency (PCE) of semitransparent devices due to the reduced optical loss. The universality of the PPHJ structure in the preparation of ST-OSCs is proved. Furthermore, an inset of a superhydrophobic patterned soft insertion layer (PSIL) in the encapsulated window improves the waterproof performance without losing transparency. Accordingly, the semitransparent devices based on the 2,2'-((2Z,2'Z)-((12,13-bis(2-ethylhexyl)-3,9-diundecyl-12,13-dihydro-[1,2,5]thiadiazolo[3,4-e]thieno[2″,3″:4',5']thieno[2',3':4,5]pyrrolo[3,2-g]thieno[2',3':4,5]thieno[3,2-b]indole-2,10-diyl)bis(methanylylidene))bis(5,6-difluoro-3-oxo-2,3-dihydro-1H-indene-2,1-diylidene))dimalononitrile (Y6) system afford a maximal efficiency of 14.62%, with a considerable AVT of 20.42%, and the resultant solar windows achieve a stabilized efficiency of 13.34% with excellent waterproof performance. Moreover, the PCE of the unilateral broken solar windows retains 70.6% of the initial efficiency after being placed under simulated rainfall conditions for 1200 h at room temperature.

A novel method to reconstruct right recurrent laryngeal nerve by transforming into nonrecurrent laryngeal nerve: The end-to-free vagal laryngeal branch end anastomosis.

The objective of this study is to demonstrate a novel method for the reconstruction of right recurrent laryngeal nerve (RLN) by transforming into nonrecurrent RLN: the end-to-free vagal laryngeal branch end anastomosis. Here we report a case of locally advanced thyroid carcinoma. The patient underwent radical thyroid surgery with inevitably partial RLN resection and immediate right RLN reconstruction at our institution. With the guidance of intraoperative neuromonitoring (IOMN), we completed a novel end-to-free vagal laryngeal branch end anastomosis. The whole procedure was deliberately monitored by IOMN. Surgeons can procure adequate free nerve for tension-free anastomosis by transforming the right RLN into nonrecurrent nerve. Follow-up laryngoscope showed improved adductory movement of the right arytenoid. The end-to-free vagal end anastomosis is an effective way to reconstruct segmental nerve resection of right RLN. Its long-term postoperative result needs to be further warranted.

Defect Passivation Effect of Chemical Groups on Perovskite Solar Cells.

Defect passivation is a key strategy to prepare high-performance perovskite solar cells (PVSCs). Even though abundant passivation molecules have been applied, the absence of detailed researches with regard to different functional groups in polymer additives may inevitably impede the establishment of passivation molecules selection rules. In this work, three passivation molecules including poly(vinyl alcohol) (PVA), polymethyl acrylate (PMA), and poly(acrylic acid) (PAA) are employed to systematically analyze the passivation effect from hydroxyl, carbonyl, and carboxyl groups. In general, PVA (-OH) can form hydrogen bonds with perovskite and PMA (-C═O) can complex with uncoordinated Pb2+. Specifically, PAA (-COOH) can interact selectively with MA+ and I- ions via hydrogen bonding and complex with uncoordinated Pb2+ to passivate defects more effectively. Hence, the PAA-incorporated PVSCs based on MAPbI3 achieve the champion power conversion efficiency (PCE) of 20.29% with open-circuit voltage up to 1.13 V. In addition, PAA cross-linking perovskite grains can relieve mechanical stress, as well as occupy the major channels to suppress ion migration and water/oxygen erosion. The corresponding unencapsulated devices demonstrate a superior light soaking stability, retaining more than 80% of the original PCE under one sun illumination for 1000 h.

Diammonium Molecular Configuration-Induced Regulation of Crystal Orientation and Carrier Dynamics for Highly Efficient and Stable 2D/3D Perovskite Solar Cells.

The effects from the molecular configuration of diammonium spacer cations on 2D/3D perovskite properties are still unclear. Here, we investigated systematically the mechanism of molecular configuration-induced regulation of crystallization kinetic and carrier dynamics by employing various diammonium molecules to construct Dion-Jacobson (DJ)-type 2D/3D perovskites to further facilitating the photovoltaic performance. The minimum average Pb-I-Pb angle leads to the smallest octahedral tilting of [PbX6 ]4- lattice in optimal diammonium molecule-incorporated DJ-type 2D/3D perovskite, which enables suitable binding energy and hydrogen-bonding between spacer cations and inorganic [PbX6 ]4- cages, thus contributing to the formation of high-quality perovskite film with vertical crystal orientation, mitigatory lattice distortion and efficient carrier transportation. As a consequence, a dramatically improved device efficiency of 22.68 % is achieved with excellent moisture stability.

Different clinicopathologic features predispose to different patterns of distant metastasis with heterogeneous short-term prognosis in patients with differentiated thyroid cancer.

BACKGROUND: Limited studies have focused on the associated clinicopathologic features and short-term prognostic impacts of metastatic patterns at initial diagnosis in differentiated thyroid cancer (DTC). METHODS: Overall, 530 individuals with distant DTC diagnosed between 2010 and 2014 were identified from Surveillance, Epidemiology, and End Results (SEER) database. Multinomial logistic regression model was used to assess the clinicopathologic factors influencing the pattern of distant metastasis. Kaplan-Meier method and multivariable Cox regression were used to estimate the short-term effects of metastatic patterns on overall (OS) and thyroid cancer-specific survival (TCSS). RESULTS: Fifty, 111, 263, 59 and 47 patients presented with distant lymph node (LN)-only, bone-only, lung-only, bone plus lung, and liver and/or brain metastases (Mets), respectively. Regional lymph node metastasis (LNM) and follicular histotype were the only confirmed risk factors for distant LN-only Mets and bone-only Mets, respectively. Larger tumour size, extrathyroidal extension (ETE) and papillary histotype were associated with lung-only Mets. Synchronous bone and lung Mets were more likely to occur in older patients. In addition, patients with distant LN-only Mets had hardly any negative effect on OS and TCSS, whereas those with synchronous bone and lung or liver/brain Mets predicted unfavourable short-term outcomes, regardless of whether they received total thyroidectomy and radioisotopes. CONCLUSIONS: Different clinicopathologic factors predispose to different patterns of metastases with profound short-term survival differences among DTC patients. Our findings may help to determine effective pretreatment screening for aggressive metastatic patterns at initial diagnosis, and thus to provide additional treatment or access of clinical trials for these patients.

Single-cell transcriptomic analysis of the tumor ecosystems underlying initiation and progression of papillary thyroid carcinoma.

The tumor ecosystem of papillary thyroid carcinoma (PTC) is poorly characterized. Using single-cell RNA sequencing, we profile transcriptomes of 158,577 cells from 11 patients' paratumors, localized/advanced tumors, initially-treated/recurrent lymph nodes and radioactive iodine (RAI)-refractory distant metastases, covering comprehensive clinical courses of PTC. Our data identifies a "cancer-primed" premalignant thyrocyte population with normal morphology but altered transcriptomes. Along the developmental trajectory, we also discover three phenotypes of malignant thyrocytes (follicular-like, partial-epithelial-mesenchymal-transition-like, dedifferentiation-like), whose composition shapes bulk molecular subtypes, tumor characteristics and RAI responses. Furthermore, we uncover a distinct BRAF-like-B subtype with predominant dedifferentiation-like thyrocytes, enriched cancer-associated fibroblasts, worse prognosis and promising prospect of immunotherapy. Moreover, potential vascular-immune crosstalk in PTC provides theoretical basis for combined anti-angiogenic and immunotherapy. Together, our findings provide insight into the PTC ecosystem that suggests potential prognostic and therapeutic implications.