T-cell receptor (TCR)
The T-cell receptor (TCR) is a membrane-bound antigen receptor expressed by T lymphocytes and is central to adaptive immunity.
The T-cell receptor (TCR) is a membrane-bound antigen receptor expressed by T lymphocytes and is central to adaptive immunity. It recognizes antigenic peptides presented by major histocompatibility complex molecules, enabling T cells to detect infected, malignant, or otherwise altered cells. In this way, TCR specificity underlies T-cell activation, tolerance, effector function, and the distinction between productive immune responses and anergic or nonresponsive states.
Structurally and functionally, TCRs are most often discussed in the context of their variable regions, especially the complementarity-determining region 3 (CDR3), which contributes strongly to antigen specificity. Because conventional TCR recognition is often HLA-restricted and depends on peptide-MHC affinity and avidity, the receptor is a major focus in cancer immunotherapy, infectious disease research, and immune engineering. Recent work has also expanded TCR research into single-cell and spatial multi-omics, computational binding prediction, and engineered cell therapies, including T-cell receptor gene transfer alongside chimeric antigen receptor approaches.
Where the papers sit
11 papers from the last 6 months study T-cell receptor (TCR) directly · updated from PubMed 10 Oct 2026
Study type 0 clinical trials · 2 human data · 7 preclinical · 2 unclassified
Themes one subject · 1 paradigm shift · 1 new direction
Those 11 are all about one subject.
-
TCR-Based Cancer Immunotherapy
TCR therapy is moving toward broader, more scalable targeting of heterogeneous solid tumors and hematologic cancers. Bispecific TCR engagers, neoantigen and metabolite-reactive receptor discovery, and hematopoietic stem cell engineering aim to produce potent off-the-shelf products. Machine-learning specificity prediction and clonotype-resolved multi-omics support receptor selection and functional monitoring. Checkpoint blockade, IFNγ-driven ferroptosis, and engineered CAR-T features add complementary routes to overcome immune escape.
Antigen heterogeneity need not remain a terminal limitation of antigen-specific TCR therapy
The KRAS-G12V/Trop2 TCR-JANUS engager study and the MART-1-specific TCR-T/RSL3 melanoma heterogeneity study both treated antigenically heterogeneous tumors, but found that antigen-divergent escape could be eliminated by adding a second killing route: TCR-JANUS redirected TCR-T cells to Trop2-positive cells while preserving cognate pHLA recognition, whereas RSL3-induced ferroptosis, enhanced by T-cell-derived IFNγ, eradicated β2-microglobulin-deficient antigen-negative cells. Together, these findings replace the assumption that TCR specificity necessarily confines therapy to cells displaying the original target and establish combination designs that extend activity across heterogeneous tumor populations 42715334Sep 42397036Jul.
Oncolytic-virus engagement of the endogenous TCR can be used to program CAR-T-cell state and durability rather than to recognize the tumor directly
The vesicular-stomatitis-virus/CAR-T solid-tumor study used the endogenous TCR as an activation and programming input for CAR-T cells, generating antiviral TCR-primed CAR-T clones with enhanced effector functions, altered activation states, greater durability, and improved antitumor activity. This assigns TCR engagement a role outside the set’s predominant uses in antigen-specific tumor recognition, TCR engineering, or repertoire measurement: it becomes a tool for fine-tuning the phenotype of cells whose tumor targeting is provided by a CAR 42247513Jun.
Papers
The 11 papers from the last 6 months that study T-cell receptor (TCR) directly, newest first, by theme and by study type. Study types come from PubMed publication types and MeSH headings.
By theme
TCR-Based Cancer Immunotherapy (11)
- TCR-JANUS engager proteins enable bispecific targeting to overcome tumor heterogeneity in TCR-T cell therapy. Science advances · 9 Sept 2026 PMID 42715334
- Generation of a highly versatile TCR bispecific scaffold optimized for targeting tumor-specific peptide-HLA antigens. mAbs · 1 Sept 2026 PMID 42680712
- Scalable generation of hematopoietic stem cell-engineered off-the-shelf mono-specific cytotoxic T cells targeting solid tumors. Cell reports. Medicine · 19 Aug 2026 PMID 42617602
- Predicting specificity of TCR-pMHC interactions using machine-learning and biophysical models. Cell systems · 13 Aug 2026 PMID 42594866
- Enhancement of Ferroptosis in Escape Variant Tumor Cells by IFNγ Derived from Antigen-Specific T Cells Controls Tumor with Heterogeneity. Cancer immunology research · 3 Jul 2026 PMID 42397036
- Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones. Cancer research · 22 Jun 2026 PMID 42329854
- circVDJ-seq for T cell clonotype detection in single-cell and spatial multi-omics. Genome medicine · 11 Jun 2026 PMID 42271498
- Engagement of the TCR against an oncolytic virus generates a population of effector CAR T cells with potent antitumor activity. Science advances · 5 Jun 2026 PMID 42247513
- Directing fratricide within T cell products using an anti-uPAR chimeric antigen receptor to drive the production of potent therapeutic cells. Molecular therapy : the journal of the American Society of Gene Therapy · 4 Jun 2026 PMID 42237538
- Harnessing Neoantigen-specific T Cells for Precision Immunotherapy in Hematologic Malignancies. Blood · 20 Apr 2026 PMID 42008381
- Universal Nanovial Screening Enables Functional Discovery of Metabolite-Reactive T-Cell Receptors for Cancer Therapy. ACS nano · 16 Apr 2026 PMID 41990155
By study type
Human data, design not indexed (2)
- Predicting specificity of TCR-pMHC interactions using machine-learning and biophysical models. Cell systems · 13 Aug 2026 PMID 42594866
- Directing fratricide within T cell products using an anti-uPAR chimeric antigen receptor to drive the production of potent therapeutic cells. Molecular therapy : the journal of the American Society of Gene Therapy · 4 Jun 2026 PMID 42237538
Preclinical: animal, cell and lab studies (7)
- TCR-JANUS engager proteins enable bispecific targeting to overcome tumor heterogeneity in TCR-T cell therapy. Science advances · 9 Sept 2026 PMID 42715334
- Generation of a highly versatile TCR bispecific scaffold optimized for targeting tumor-specific peptide-HLA antigens. mAbs · 1 Sept 2026 PMID 42680712
- Scalable generation of hematopoietic stem cell-engineered off-the-shelf mono-specific cytotoxic T cells targeting solid tumors. Cell reports. Medicine · 19 Aug 2026 PMID 42617602
- Enhancement of Ferroptosis in Escape Variant Tumor Cells by IFNγ Derived from Antigen-Specific T Cells Controls Tumor with Heterogeneity. Cancer immunology research · 3 Jul 2026 PMID 42397036
- Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones. Cancer research · 22 Jun 2026 PMID 42329854
- Engagement of the TCR against an oncolytic virus generates a population of effector CAR T cells with potent antitumor activity. Science advances · 5 Jun 2026 PMID 42247513
- Universal Nanovial Screening Enables Functional Discovery of Metabolite-Reactive T-Cell Receptors for Cancer Therapy. ACS nano · 16 Apr 2026 PMID 41990155
Unclassified: not yet indexed with MeSH (2)
- circVDJ-seq for T cell clonotype detection in single-cell and spatial multi-omics. Genome medicine · 11 Jun 2026 PMID 42271498
- Harnessing Neoantigen-specific T Cells for Precision Immunotherapy in Hematologic Malignancies. Blood · 20 Apr 2026 PMID 42008381
Written from 11 PubMed abstracts, each one listed by PMID above. Published: 2026-07-08. Last written: 2026-09-11 by GPT. Corrections: 2026-09-26 by GPT. Drafted by language models from published abstracts; not medical advice.