Read more about the article The type 2 cytokine Fc–IL-4 revitalizes exhausted CD8+ T cells against cancer
a–f, C57BL/6 mice bearing B16F10 tumours received ACT of PMEL T cells (5 × 106, i.v.) followed by administration of Fc–IL-4 (20 µg, p.t.) or PBS every other day for four doses. Mice were euthanized on day 14 and the tumour tissues were collected for analysis by flow cytometry. Data are a single representative of two independent experiments. All data represent mean ± s.e.m. Shown are the experimental timeline (a), cell counts of PMEL or endogenous CD8+ TILs (b) (n = 8 animals), representative flow cytometry plots showing the frequencies of tumour-infiltrating CD8+ TTE cells (PD-1+TIM-3+) among PMEL or endogenous CD8+ TILs (c), cell counts of three subpopulations among PMEL or endogenous CD8+ TILs (d) (n = 8 animals), and representative flow cytometry plots (e) and frequencies (f) of granzyme B+ and TNF+IFNγ+ among tumour-infiltrating CD8+ TTE cells (n = 5 animals). g–j, C57BL/6 mice bearing B16F10 tumours received ACT of PMEL T cells (5 × 106, i.v.) followed by administration of Fc–IL-4 (20 µg, p.t.) or PBS every other day for four doses in total. Mice were euthanized on day 14, tumour tissues were collected, and PMEL CD8+ T cells were sorted for scRNA-seq (n = 5 animals). g, UMAP clustering of all the PMEL CD8+ TILs. h, Indicated co-inhibitory gene marker expression on the UMAP. i, Comparison of cell proportion in each cluster. j, Comparison of functional gene expression in the terminally exhausted-like T cells. Statistical analyses are performed using two-sided unpaired Student’s t-test. Schematic in a created using BioRender (https://Biorender.com).

The type 2 cytokine Fc–IL-4 revitalizes exhausted CD8+ T cells against cancer

type 2 cytokine Fc-IL-4는 exhausted CD8+ T cell을 활성화하여 암에 대항한다 Abstract 현재의 암 면역 요법은 주로 암과 싸우는 type 1 면역 반응을 유도하는 데 중점을 두고 있지만, 장기적인 완전…

Continue ReadingThe type 2 cytokine Fc–IL-4 revitalizes exhausted CD8+ T cells against cancer
Read more about the article Single-cell CAR T atlas reveals type 2 function in 8-year leukaemia remission
a, Schematic of the experimental design. The diagram was created using BioRender. b, UMAP visualization of 695,819 high-quality single CAR T cells, filtered from 1,029,340 sequenced cells across all patients and donors. Unsupervised clustering identified 17 distinct clusters. c, The patient demographics and clinical documentation. Patients were divided into five persistence groups on the basis of their durations of BCA. The discovery cohort includes 42 patients from clinical trial NCT01626495, and the validation cohort consists of 40 patients from clinical trial NCT02906371. IPA, ingenuity pathway analysis; Tc, cytotoxic T cell; Treg, regulatory T cell.

Single-cell CAR T atlas reveals type 2 function in 8-year leukaemia remission

Single-cell CAR T 아틀라스가 8-year leukaemia remission에서 type 2 function을 밝혀낸다 Abstract Acute lymphocytic leukaemia(ALL)에 대한 chimeric antigen receptor (CAR) T cell 치료의 높은 반응률에도 불구하고 약 50%의 환자가 첫해…

Continue ReadingSingle-cell CAR T atlas reveals type 2 function in 8-year leukaemia remission

Mitochondrial complex I promotes kidney cancer metastasis

Mitochondrial complex I은 신장암 전이를 유도한다 Abstract 대부분의 신장암은 대사적인 문제를 동반하지만, 이러한 대사 기능 이상이 인간의 암 진행에 어떤 영향을 미치는지는 알려져 있지 않습니다.  이 연구에서는 신장암 수술 중…

Continue ReadingMitochondrial complex I promotes kidney cancer metastasis
Read more about the article In vivo interaction screening reveals liver-derived constraints to metastasis
a, Schematic of the screen. DTCs interact with hepatocytes harbouring seeding-promoting or seeding-suppressing perturbations, influencing local metastatic outgrowth and therefore sgRNA enrichment in metastasis-proximal hepatocytes. b, Genes ranked by proximal enrichment score. Seeding-promoting factors are enriched in GFP+mCherry+ hepatocytes (red). Suppressing factors are enriched in GFP+mCherry− hepatocytes (green). Top-scoring SRFs are listed on the right. c, The log-transformed fold change (FC) of individual sgRNAs (vertical lines) for two suppressing and two promoting factors across all mice (n = 7) and library batches (n = 3). d, GSEA of SRFs. The dot size indicates the gene set size. e, Interaction analysis in a human CRC liver metastasis. 22 SRFs expressed by metastasis-proximal hepatocytes (orange) are predicted to interact with LRs on tumour cells at the metastatic leading edge (turquoise). f, Predicted interactions between SRFs and LRs that are frequently mutated in liver metastases. CNV status is shown in orange (amplified), yellow (mutation) or blue (deleted). g, Representative fluorescence micrograph showing co-culture of Alb-cre;dCas9-SPH hepatocytes overexpressing SRFs (GFP+) and AKPSsLP-mCherry colonies (mCherry+, arrowheads). Scale bar, 100 μm. h–k, The CFU per well of AKPSsLP-mCherry organoids co-cultured with AML12dCas9-SPH cells overexpressing SRFs (n = 3 wells; h), AKPSsLP-mCherry organoids co-cultured with AML12 cells overexpressing Plxnb2 (n = 10 wells; i), AKPSsLP-mCherry organoids treated with rmPlexin B2 (n = 3 wells; j) and PDOs treated with rhPlexin B2 (n = 5 wells; k). Statistical analysis was performed using ordinary one-way analysis of variance (ANOVA) with Dunnet’s correction for multiple testing (h–j) or two-tailed unpaired t-tests (k). Data are mean ± s.d. For b–d, results are pooled from three independent experiments.

In vivo interaction screening reveals liver-derived constraints to metastasis

In vivo 상호작용 screening은 전이에 대한 간 유래 constraints를 밝혀낸다 Abstract 전이된 암 세포 중 단 0.02%만이 *명확한 전이(overt metastasis)를 일으킬(seed) 수 있는 것으로 추정된다. 이는 전이의 seeding에 대한 환경적…

Continue ReadingIn vivo interaction screening reveals liver-derived constraints to metastasis

Spatiotemporally resolved colorectal oncogenesis in mini-colons ex vivo

시험관 내 소형 대장 모델을 통해 시공간적으로 해석된 대장암 발생 과정 관찰 Abstract 3차원 오가노이드 배양 기술은 종양 및 미세환경 구조를 보다 현실적이고 확장 가능하게 재현할 수 있게 하여 암…

Continue ReadingSpatiotemporally resolved colorectal oncogenesis in mini-colons ex vivo

Evolutionary trajectories of small cell lung cancer under therapy

치료 중 소세포 폐암의 진화 과정 Abstract 소세포 폐암(Small cell lung cancer; SCLC)은 화학요법에 대해 뚜렷한 민감성을 보이는 동시에, 빠르게 재발하는 경향이 있지만, 이와 관련된 진화적 과정은 아직 명확히 알려지지…

Continue ReadingEvolutionary trajectories of small cell lung cancer under therapy

Inherited blood cancer predisposition through altered transcription elongation

변형된 전사 연장을 통한 유전된 혈액암의 경향 Abstract 골수 악성종양을 일으키는 다양한 체세포 돌연변이를 정의하는 데 진전이 있었지만, 이러한 암에 대한 중요한 유전적 성분은 대부분 설명되지 않았습니다. 이 연구에서는 대형…

Continue ReadingInherited blood cancer predisposition through altered transcription elongation
Read more about the article A TCF4-dependent gene regulatory network confers resistance to immunotherapy in melanoma
Highlights • Drug-naive human melanomas contain cancer cells in a MES state • Melanoma cells in the MES state are enriched in on-treatment lesions refractory to ICB • TCF4 promotes the MES while suppressing the melanocytic and antigen presentation programs • Targeting TCF4 expression increases sensitivity to ICB and targeted therapy

A TCF4-dependent gene regulatory network confers resistance to immunotherapy in melanoma

*면역 체크포인트 차단제(immune checkpoint blockade, ICB)에 대한 내재적 저항성을 더 잘 이해하기 위해, 우리는 치료받지 않은 melanoma 생태계의 세포 구조에 대한 포괄적인 관점을 확립하고 ICB를 투여했을 때 어떻게 진화하는지 연구했다. 단일 세포, 공간 다중 오믹스(single-cell, spatial multi-omics)를 사용하여, 우리는 **종양 미세환경(tumor microenvironment, TME)이 복잡한 melanoma transcriptomic landscape의 출현을 촉진한다는 것을 보여주었다. ***중간엽 유사(mesenchymal-like, MES) 상태를 가진 melanoma 세포, 즉 표적 치료에 대한 저항성을 부여하는 것으로 알려진 세포군은 ICB에 반응하지 않는 환자들의 초기 치료 생검에서 상당히 풍부하게 발견되었다. TCF4는 이 landscape의 허브로서 MES signature의 주요 조절자(master regulator)이자 멜라노사이트(melanocytic) 및 항원 제시(antigen presentation) transcriptional program의 억제제 역할을 한다. 유전적으로나 약물학적(bromodomain 억제제 사용)으로 TCF4를 표적하는 것은 MES 세포의 면역원성과 ICB 및 표적 치료에 대한 민감도를 증가시켰다. 따라서, 우리는 여러 transcriptional program을 조정하고 melanoma에서 표적 치료와 ICB에 대한 저항성에 기여하는 TCF4 의존적 규제 네트워크를 밝혀냈다.

Continue ReadingA TCF4-dependent gene regulatory network confers resistance to immunotherapy in melanoma

Clinical trial links oncolytic immunoactivation to survival in glioblastoma

교모세포종(glioblastoma) 생존율과 연결된 온콜리틱(oncolytic) 면역 활성화*에 관한 임상 시험 Abstract 면역 요법 실패는 재발성 교모세포종(rGBM)과 같은 공격적인 형태의 암을 특징짓는 매우 억제적인 종양 미세환경에서 비롯될 수 있습니다. 여기서 우리는 재발성…

Continue ReadingClinical trial links oncolytic immunoactivation to survival in glioblastoma

Epigenetic regulation during cancer transitions across 11 tumour types

11가지 tumour 유형에서 암으로 변화하는 과정의 epigenetic 조절 Abstract Chromatin accessibility는 유전자 발현 조절 및 세포 정체성(Cellular identity)에 필수적이며, accessibility의 변화는 암의 시작, 진행 및 metastasis를 촉진하는 것과 관련이 있다.…

Continue ReadingEpigenetic regulation during cancer transitions across 11 tumour types