Selective recovery of pyrolyzates of biodegradable (PLA, PHBH) and common plastics (HDPE, PP, PS) during co-pyrolysis under slow heating.

Pyrolytic synergistic interactions, in which the production of pyrolyzates is enhanced or inhibited, commonly occur during the co-pyrolysis of different polymeric materials, such as plastics and biomass. Although these interactions can increase the yield of desired pyrolysis products under controlled degradation conditions, the desired compounds must be separated from complex pyrolyzates and further purified. To balance these dual effects, this study was aimed at examining pyrolytic synergistic interactions during slow heating co-pyrolysis of biodegradable plastics including polylactic acid (PLA) and poly(3-hydroxybutyrate-co-3-hydroxyhexaoate) (PHBH) and petroleum-based plastics including high-density polyethylene (HDPE), polypropylene (PP), and polystyrene (PS). Comprehensive investigations based on thermogravimetric analysis, pyrolysis-gas chromatography/mass spectrometry, and evolved gas analysis-mass spectrometry revealed that PLA and PHBH decompose at lower temperatures (273-378 °C) than HDPE, PP, and PS (386-499 °C), with each polymer undergoing independent decomposition without any pyrolytic interactions. Thus, the independent pyrolysis of biodegradable plastics, such as PLA and PHBH, with common plastics, such as HDPE, PP, and PS, can theoretically be realized through temperature control, enabling the selective recovery of their pyrolyzates in different temperature ranges. Thus, pyrolytic approaches can facilitate the treatment of mixed biodegradable and common plastics.

Definitive chemoradiotherapy induces T-cell-inflamed tumor microenvironment in unresectable locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Chemoradiotherapy (CRT) modulates the tumor immune microenvironment of multiple cancer types, including esophageal cancer, which potentially induces both immunogenicity and immunosuppression by upregulating the presentation of tumor-specific antigens and immune checkpoint molecules in tumors, respectively. The prognostic effects of immune modification by CRT in esophageal squamous cell carcinoma (ESCC) remain controversial because of the lack of detailed immunological analyses using paired clinical specimens before and after CRT. We aimed to clarify the immunological changes in the tumor microenvironment caused by CRT and elucidate the predictive importance of clinical response and prognosis and the rationale for the necessity of subsequent programmed cell death protein 1 (PD-1) inhibitor treatment. METHODS: In this study, we performed a comprehensive immunological analysis of paired biopsy specimens using multiplex immunohistochemistry before and after CRT in patients with unresectable locally advanced ESCC. RESULTS: CRT significantly increased the intra-tumoral infiltration and PD-1 expression of CD8+ T cells and conventional CD4+ T cells but decreased those of regulatory T cells and the accumulation of tumor-associated macrophages. Multivariate analysis of tumor-infiltrating T-cell phenotypes revealed that the density of PD-1+CD8+ T cells in the tumor after CRT could predict a confirmed complete response and favorable survival. CONCLUSIONS: This study showed that CRT improved the immunological characteristics of unresectable locally advanced ESCC and identified the density of PD-1+CD8+ T cells as a predictive factor for prognosis. This finding supports the rationale for the necessity of subsequent PD-1 inhibitor treatment.

LTK mutations responsible for resistance to lorlatinib in non-small cell lung cancer harboring CLIP1-LTK fusion.

The CLIP1-LTK fusion was recently discovered as a novel oncogenic driver in non-small cell lung cancer (NSCLC). Lorlatinib, a third-generation ALK inhibitor, exhibited a dramatic clinical response in a NSCLC patient harboring CLIP1-LTK fusion. However, it is expected that acquired resistance will inevitably develop, particularly by LTK mutations, as observed in NSCLC induced by oncogenic tyrosine kinases treated with corresponding tyrosine kinase inhibitors (TKIs). In this study, we evaluate eight LTK mutations corresponding to ALK mutations that lead to on-target resistance to lorlatinib. All LTK mutations show resistance to lorlatinib with the L650F mutation being the highest. In vitro and in vivo analyses demonstrate that gilteritinib can overcome the L650F-mediated resistance to lorlatinib. In silico analysis suggests that introduction of the L650F mutation may attenuate lorlatinib-LTK binding. Our study provides preclinical evaluations of potential on-target resistance mutations to lorlatinib, and a novel strategy to overcome the resistance.

Regulatory T cell-mediated immunosuppression orchestrated by cancer: towards an immuno-genomic paradigm for precision medicine.

Accumulating evidence indicates that aberrant signalling stemming from genetic abnormalities in cancer cells has a fundamental role in their evasion of antitumour immunity. Immune escape mechanisms include enhanced expression of immunosuppressive molecules, such as immune-checkpoint proteins, and the accumulation of immunosuppressive cells, including regulatory T (Treg) cells, in the tumour microenvironment. Therefore, Treg cells are key targets for cancer immunotherapy. Given that therapies targeting molecules predominantly expressed by Treg cells, such as CD25 or GITR, have thus far had limited antitumour efficacy, elucidating how certain characteristics of cancer, particularly genetic abnormalities, influence Treg cells is necessary to develop novel immunotherapeutic strategies. Hence, Treg cell-targeted strategies based on the particular characteristics of cancer in each patient, such as the combination of immune-checkpoint inhibitors with molecularly targeted agents that disrupt the immunosuppressive networks mediating Treg cell recruitment and/or activation, could become a new paradigm of cancer therapy. In this Review, we discuss new insights on the mechanisms by which cancers generate immunosuppressive networks that attenuate antitumour immunity and how these networks confer resistance to cancer immunotherapy, with a focus on Treg cells. These insights lead us to propose the concept of 'immuno-genomic precision medicine' based on specific characteristics of cancer, especially genetic profiles, that correlate with particular mechanisms of tumour immune escape and might, therefore, inform the optimal choice of immunotherapy for individual patients.

Recent Advancements in Pyrolysis of Halogen-Containing Plastics for Resource Recovery and Halogen Upcycling: A State-of-the-Art Review.

Plastic waste has emerged as a serious issue due to its impact on environmental degradation and resource scarcity. Plastic recycling, especially of halogen-containing plastics, presents challenges due to potential secondary pollution and lower-value implementations. Chemical recycling via pyrolysis is the most versatile and robust approach for combating plastic waste. In this Review, we present recent advancements in halogen-plastic pyrolysis for resource utilization and the potential pathways from "reducing to recycling to upcycling" halogens. We emphasize the advanced management of halogen-plastics through copyrolysis with solid wastes (waste polymers, biomass, coal, etc.), which is an efficient method for dealing with mixed wastes to obtain high-value products while reducing undesirable substances. Innovations in catalyst design and reaction configurations for catalytic pyrolysis are comprehensively evaluated. In particular, a tandem catalysis system is a promising route for halogen removal and selective conversion of targeted products. Furthermore, we propose novel insights regarding the utilization and upcycling of halogens from halogen-plastics. This includes the preparation of halogen-based sorbents for elemental mercury removal, the halogenation-vaporization process for metal recovery, and the development of halogen-doped functional materials for new materials and energy applications. The reutilization of halogens facilitates the upcycling of halogen-plastics, but many efforts are needed for mutually beneficial outcomes. Overall, future investigations in the development of copyrolysis and catalyst-driven technologies for upcycling halogen-plastics are highlighted.

Metabolic advantages of regulatory T cells dictated by cancer cells.

Cancer cells employ glycolysis for their survival and growth (the "Warburg effect"). Consequently, surrounding cells including immune cells in the tumor microenvironment (TME) are exposed to hypoglycemic, hypoxic, and low pH circumstances. Since effector T cells depend on the glycolysis for their survival and functions, the metabolically harsh TME established by cancer cells is unfavorable, resulting in the impairment of effective antitumor immune responses. By contrast, immunosuppressive cells such as regulatory T (Treg) cells can infiltrate, proliferate, survive, and exert immunosuppressive functions in the metabolically harsh TME, indicating the different metabolic dependance between effector T cells and Treg cells. Indeed, some metabolites that are harmful for effector T cells can be utilized by Treg cells; lactic acid, a harmful metabolite for effector T cells, is available for Treg cell proliferation and functions. Deficiency of amino acids such as tryptophan and glutamine in the TME impairs effector T cell activation but increases Treg cell populations. Furthermore, hypoxia upregulates fatty acid oxidation via hypoxia-inducible factor 1α (HIF-1α) and promotes Treg cell migration. Adenosine is induced by the ectonucleotidases CD39 and CD73, which are strongly induced by HIF-1α, and reportedly accelerates Treg cell development by upregulating Foxp3 expression in T cells via A2AR-mediated signals. Therefore, this review focuses on the current views of the unique metabolism of Treg cells dictated by cancer cells. In addition, potential cancer combination therapies with immunotherapy and metabolic molecularly targeted reagents that modulate Treg cells in the TME are discussed to develop "immune metabolism-based precision medicine".

Latest trends and challenges in PVC and copper recovery technologies for End-of-Life thin cables.

This review investigates the latest trends in separation technologies regarding hard-to-recycle thin cables, specifically in the form of end-of-life wire harnesses (WHs). The cables in WHs mainly contain copper (Cu) and poly(vinyl chloride) (PVC), which is commonly used to insulate and sheath cables. This review reveals that most separation technologies prioritize the recovery of Cu and overlook that of PVC. The recovery of high-purity PVC is very important because of its incompatibility with other plastics or Cu during recycling treatments. Through this investigation, we confirm that physical treatments, such as stripping and chopping, are insufficient to recover high-purity PVC from thin cables. Instead, a combination of chemical (e.g., swelling of PVC insulation or sheathing of cables under a suitable solvent) and physical (e.g., ball or rod milling and mechanical agitation of swollen cables) treatments can be used to achieve the recovery of high-purity PVC and Cu both for recycling. We believe that recovering metals and plastics from end-of-life cables is vital for sustainable waste management, offering several environmental and economic benefits.

Precise patient stratification in esophageal cancer: Biomarkers for immunochemotherapy.

Studies have established immunochemotherapy as the first-line treatment for advanced esophageal cancer. Chen et al. and Carrol et al. performed exploratory analysis of the JUPITER-06 and LUD2015-005 trials, respectively and identified biomarkers to predict therapy response based on immunogenomic analysis. These findings may optimize precise patient stratification in advanced esophageal cancer.

The EGFR C797S Mutation Confers Resistance to a Novel EGFR Inhibitor CLN-081 to EGFR Exon 20 Insertion Mutations.

Introduction: EGFR exon 20 insertion mutations account for 5% to 10% of EGFR-mutated NSCLC. CLN-081 (formerly known as TAS6417), a novel covalent EGFR tyrosine kinase inhibitor, exhibits pan-mutation selective efficacy, including exon 20 insertions, in the clinical setting. Nevertheless, some patients may not respond to CLN-081 and resistance to CLN-081 may emerge over time in others. Methods: We exposed Ba/F3 cells transduced with EGFR exon 20 insertions (Y764_V765 insHH or A767_S768insSVD) to increasing concentrations of CLN-081 to generate resistant cells and then subjected their complementary DNA to sequencing to identify acquired mutations. We then evaluated effects of small molecules on engineered Ba/F3 cells on the basis of proliferation assays, Western blotting, and xenograft models. Results: All CLN-081 resistant clones harbored the EGFR C797S mutation. Ba/F3 cells with C797S (Ba/F3-C797S) were resistant to EGFR tyrosine kinase inhibitors targeting EGFR exon 20 insertion mutations, including CLN-081. Pimitespib, a selective heat shock protein 90 inhibitor, induced apoptosis in Ba/F3-C797S cells in vitro and inhibited growth of Ba/F3-C797S tumors in vivo. Ba/F3 cells with A763_Y764insFQEA-C797S remained sensitive to erlotinib. Conclusions: We conclude that the EGFR C797S mutation confers resistance to CLN-081. Our preclinical data suggest a potential small molecule to overcome CLN-081 resistance, which may benefit patients with lung cancer with EGFR exon 20 insertions.

Carbon footprint analysis and carbon neutrality potential of desalination by electrodialysis for different applications.

Low-carbon water production technologies are indispensable for achieving sustainable development goals and mitigating global climate change. However, at present, many advanced water treatment processes lack a systematic assessment of related greenhouse gas (GHG) emissions. Thus, quantifying their life-cycle GHG emissions and proposing strategies toward carbon neutrality is urgently needed. This case study focuses on electrodialysis (ED), an electricity-driven desalination technology. To analyze the carbon footprint of ED desalination in various applications, a life cycle assessment model was developed based on industrial-scale ED processes. For seawater desalination, the carbon footprint is 59.74 kg CO2-eq/metric ton removed salt, which is one order of magnitude lower than that of high-salinity wastewater treatment and organic solvent desalination. Meanwhile, the power consumption during operation is the main hotspot of GHG emissions. Power grid decarbonization and improved waste recycling in China are projected to reduce the carbon footprint up to 92%. Meanwhile, the contribution of operation power consumption is expected to reduce from 95.83% to 77.84% for organic solvent desalination. Through sensitivity analysis, significant non-linear impacts of process variables on the carbon footprint were determined. Therefore, it is recommended to optimize the process design and operation to reduce power consumption based on the current fossil-based grid. GHG reduction for module production and disposal should also be emphasized. This method can be extended to general water treatment or other industrial technologies for carbon footprint assessment and reducing GHG emission.

Complete response to definitive chemoradiotherapy in unresectable locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Although definitive chemoradiotherapy (CRT) is the standard therapy for patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC), poor survival has been reported. Although the complete response (CR) rate is strongly correlated with good prognosis, the predictive factors for CR have not been elucidated. METHODS: This registry study aimed to identify predictors of CR to definitive CRT in patients with unresectable locally advanced ESCC. "Unresectable" was defined as the primary lesion invading unresectable adjacent structures such as the aorta, vertebral body, and trachea (T4b), or the regional and/or supraclavicular lymph nodes invading unresectable adjacent structures (LNT4b). RESULTS: Overall, 175 patients who started definitive CRT between January 2013 and March 2020 were included. The confirmed CR (cCR) rate was 24% (42/175). The 2-year progression-free survival (PFS) and overall survival (OS) rates of cCR cases vs. non-cCR cases were 59% vs. 2% (log-rank p < 0.001) and 90% vs. 31% (log-rank p < 0.001), with a median follow-up period of 18.5 and 40.5 months, respectively. Multivariate analysis of clinicopathological factors revealed that tumor length ≥ 6 cm [odds ratio (OR) 0.446; 95% CI 0.220-0.905; p = 0.025] was a predictor of cCR. CONCLUSIONS: Favorable PFS and OS rates were observed in patients with cCR. Tumor length was a predictive factor for cCR.

BATF epigenetically and transcriptionally controls the activation program of regulatory T cells in human tumors.

Regulatory T (Treg) cells suppress effective antitumor immunity in tumor-bearing hosts, thereby becoming promising targets in cancer immunotherapy. Despite the importance of Treg cells in tumor immunity, little is known about their differentiation process and epigenetic profiles in the tumor microenvironment (TME). Here, we showed that Treg cells in the TME of human lung cancers harbored a completely different open chromatin profile compared with CD8+ T cells, conventional CD4+ T cells in the TME, and peripheral Treg cells. The integrative sequencing analyses including ATAC, single-cell RNA, and single-cell ATAC sequencing revealed that BATF, IRF4, NF-κB, and NR4A were important transcription factors for Treg cell differentiation in the TME. In particular, BATF was identified as a key regulator, which leveraged Treg cell differentiation through epigenetically controlling activation-associated gene expression, resulting in the robustness of Treg cells in the TME. The single-cell sequencing approaches also revealed that tissue-resident and tumor-infiltrating Treg cells followed a common pathway for differentiation and activation in a BATF-dependent manner heading toward Treg cells with the most differentiated and activated phenotypes in tissues and tumors. BATF deficiency in Treg cells remarkably inhibited tumor growth, and high BATF expression was associated with poor prognosis in lung cancer, kidney cancer, and melanoma. These findings indicate one of the specific chromatin remodeling and differentiation programs of Treg cells in the TME, which can be applied in the development of Treg cell-targeted therapies.

Evaluation of Keratin-Cellulose Blend Fibers as Precursors for Carbon Fibers.

One main challenge to utilize cellulose-based fibers as the precursor for carbon fibers is their inherently low carbon yield. This study aims to evaluate the use of keratin in chicken feathers, a byproduct of the poultry industry generated in large quantities, as a natural charring agent to improve the yield of cellulose-derived carbon fibers. Keratin-cellulose composite fibers are prepared through direct dissolution of the pulp and feather keratin in the ionic liquid 1,5-diazabicyclo[4.3.0]non-5-enium acetate ([DBNH]OAc) and subsequent dry jet wet spinning (so-called Ioncell process). Thermogravimetric analysis reveals that there is an increase in the carbon yield by ∼53 wt % with 30 wt % keratin incorporation. This increase is comparable to the one observed for lignin-cellulose composite fibers, in which lignin acts as a carbon booster due to its higher carbon content. Keratin, however, reduces the mechanical properties of cellulose precursor fibers to a lesser extent than lignin. Keratin introduces nitrogen and induces the formation of pores in the precursor fibers and the resulting carbon fibers. Carbon materials derived from the keratin-cellulose composite fiber show potential for applications where nitrogen doping and pores or voids in the carbon are desirable, for example, for low-cost bio-based carbons for energy harvest or storage.

Isolation of tumor-infiltrating lymphocytes from preserved human tumor tissue specimens for downstream characterization.

Immunophenotyping of tumor-infiltrating lymphocytes (TILs) by flow cytometry can predict clinical efficacy of immunotherapy. However, several obstacles need to be overcome for developing a flow cytometry assay starting from solid tumor specimens. Here, we show a detailed enzyme-based protocol to isolate TILs from human tumor tissues. The protocol was optimized to obtain enough viable TILs from a biopsy tissue specimen for flow cytometry-based TIL immunophenotyping. Additionally, tissue samples could be preserved for up to 72 h for subsequent characterization. For complete details on the use and execution of this protocol, please refer to Kumagai et al. (2020, 2022).

An integrated utilization strategy of printed circuit boards and waste tire by fast co-pyrolysis: Value-added products recovery and heteroatoms transformation.

Fast co-pyrolysis has been suggested as a promising technique to solve the environmental issues and simultaneously recover value-added products from polymer wastes. However, to date, no studies have focused on fast co-pyrolysis of printed circuit boards (PCB) and waste tire (WT). Therefore, we comprehensively investigated the fast co-pyrolysis of PCB and WT using pyrolysis-gas chromatography/mass spectrometry. The results show that an increase in temperature during fast pyrolysis improved the interactions between the PCB and WT pyrolyzates, increasing the formation of aliphatic and aromatic compounds. The formation of p-cymene was greatly induced by the isomerization and dehydrogenation reactions of D-limonene. Co-pyrolysis reduced the formation of brominated phenols and benzothiazole from PCB and WT pyrolysis, respectively, whereas promoted the interactions between Br- and S/N-containing radicals, concentrating them into heavy compounds. Increasing the temperature enhanced the release of heteroatom compounds. The findings suggest that debromination of PCB achieved via dehydrogenation of WT pyrolysis provoked secondary reactions of olefins and interactions of heteroatom radicals. The major products were accurately predicted by different fitting models using response surface methodology, indicating the synergistic interactions during co-pyrolysis. The results were beneficial for optimizing the experimental parameters to obtain the maximum yield of desired products.

Study protocol for JCOG1807C (DEEP OCEAN): a interventional prospective trial to evaluate the efficacy and safety of durvalumab before and after operation or durvalumab as maintenance therapy after chemoradiotherapy against superior sulcus non-small cell lung cancer.

BACKGROUND: Superior sulcus tumours (SSTs) are relatively uncommon and one of the most intractable lung cancers among non-small cell lung cancer (NSCLC). We planned a multicenter, single-arm confirmatory trial of new multidisciplinary treatment using immune-checkpoint inhibitor. The aim is to evaluate the safety and efficacy of new multidisciplinary treatment with perioperative durvalumab after chemoradiotherapy (CRT). METHODS: The primary endpoint is 3-year overall survival. Patients receive induction CRT with sequential two courses of durvalumab, followed by surgical resection for resectable SST. The regimen for CRT is two courses of cisplatin and S-1, and concurrent radiotherapy (66 Gy/33 Fr). After surgery, 22 courses of post-operative durvalumab therapy are administered. For unresectable SST, an additional 22 courses of durvalumab are administered after induction durvalumab. RESULTS: In two cases as a safety cohort, the safety of intervention treatment up to 30 days after surgery was examined, and there were no special safety signals. Patient enrollment has now resumed in the main cohort. CONCLUSIONS: The results of this study may contribute to the establishment of a new standard of care for SST, which is an intractable NSCLC.

Lactic acid promotes PD-1 expression in regulatory T cells in highly glycolytic tumor microenvironments.

The balance of programmed death-1 (PD-1)-expressing CD8+ T cells and regulatory T (Treg) cells in the tumor microenvironment (TME) determines the clinical efficacy of PD-1 blockade therapy through the competition of their reactivation. However, factors that determine this balance remain unknown. Here, we show that Treg cells gain higher PD-1 expression than effector T cells in highly glycolytic tumors, including MYC-amplified tumors and liver tumors. Under low-glucose environments via glucose consumption by tumor cells, Treg cells actively absorbed lactic acid (LA) through monocarboxylate transporter 1 (MCT1), promoting NFAT1 translocation into the nucleus, thereby enhancing the expression of PD-1, whereas PD-1 expression by effector T cells was dampened. PD-1 blockade invigorated the PD-1-expressing Treg cells, resulting in treatment failure. We propose that LA in the highly glycolytic TME is an active checkpoint for the function of Treg cells in the TME via upregulation of PD-1 expression.

The CLIP1-LTK fusion is an oncogenic driver in non-small-cell lung cancer.

Lung cancer is one of the most aggressive tumour types. Targeted therapies stratified by oncogenic drivers have substantially improved therapeutic outcomes in patients with non-small-cell lung cancer (NSCLC)1. However, such oncogenic drivers are not found in 25-40% of cases of lung adenocarcinoma, the most common histological subtype of NSCLC2. Here we identify a novel fusion transcript of CLIP1 and LTK using whole-transcriptome sequencing in a multi-institutional genome screening platform (LC-SCRUM-Asia, UMIN000036871). The CLIP1-LTK fusion was present in 0.4% of NSCLCs and was mutually exclusive with other known oncogenic drivers. We show that kinase activity of the CLIP1-LTK fusion protein is constitutively activated and has transformation potential. Treatment of Ba/F3 cells expressing CLIP1-LTK with lorlatinib, an ALK inhibitor, inhibited CLIP1-LTK kinase activity, suppressed proliferation and induced apoptosis. One patient with NSCLC harbouring the CLIP1-LTK fusion showed a good clinical response to lorlatinib treatment. To our knowledge, this is the first description of LTK alterations with oncogenic activity in cancers. These results identify the CLIP1-LTK fusion as a target in NSCLC that could be treated with lorlatinib.

Highly immunogenic cancer cells require activation of the WNT pathway for immunological escape.

PD-1 blockade exerts antitumor effects by reinvigorating tumor antigen­specific CD8+ T cells. Whereas neoantigens arising from gene alterations in cancer cells comprise critical tumor antigens in antitumor immunity, a subset of non­small cell lung cancers (NSCLCs) harboring substantial tumor mutation burden (TMB) lack CD8+ T cells in the tumor microenvironment (TME), which results in resistance to PD-1 blockade therapy. To overcome this resistance, clarifying the mechanism(s) impairing antitumor immunity in highly mutated NSCLCs is an urgent issue. Here, we showed that activation of the WNT/ß-catenin signaling pathway contributed to the development of a noninflamed TME in tumors with high TMB. NSCLCs that lacked immune cell infiltration into the TME despite high TMB preferentially up-regulated the WNT/ß-catenin pathway. Immunologic assays revealed that those patients harbored neoantigen-specific CD8+ T cells in the peripheral blood but not in the TME, suggesting impaired T cell infiltration into the TME due to the activation of WNT/ß-catenin signaling. In our animal models, the accumulation of gene mutations in cancer cells increased CD8+ T cell infiltration into the TME, thus slowing tumor growth. However, further accumulation of gene mutations blunted antitumor immunity by excluding CD8+ T cells from tumors in a WNT/ß-catenin signaling-dependent manner. Combined treatment with PD-1 blockade and WNT/ß-catenin signaling inhibitors induced better antitumor immunity than either treatment alone. Thus, we propose a mechanism-oriented combination therapy whereby immune checkpoint inhibitors can be combined with drugs that target cell-intrinsic oncogenic signaling pathways involved in tumor immune escape.

Prediction of pyrolyzate yields by response surface methodology: A case study of cellulose and polyethylene co-pyrolysis.

There are numerous combinations of biomass, plastic, and co-pyrolysis conditions. The presence of synergies, which make pyrolyzate distribution more complex, has been supported by research. In this study, the potential of response surface methodology (RSM) to predict the pyrolyzate yields affected by synergies during co-pyrolysis (500-700 °C) of cellulose and polyethylene was investigated, beyond gas, oil, and char yields. The results indicated that co-pyrolysis promoted liquid and C5-28 hydrocarbon production with increasing temperature. The quadratic model could predict the total gas, CO, CO2, and liquid yields, including the synergy. The cubic model could predict the levoglucosan and C5-28 hydrocarbon yields due to various synergies under different conditions. The linear model was suitable for the char yield distribution without interaction. Thus, this study reveals that RSM has a significant potential to predict pyrolyzate yields, enabling co-pyrolysis condition setting to maximize the desired product recovery with the fewest experiments.