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10.1136/jitc-2025-012209 http://scihub22266oqcxt.onion/10.1136/jitc-2025-012209 40907998!12414154!40907998     free     free     free Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 263.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\40907998.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       J+Immunother+Cancer 2025 ; 13 (9): ä Nephropedia Template TP {{tp|p=40907998|t=2025. The spontaneous neoantigen-specific CD4(+) T-cell response to a growing tumor is functionally and phenotypically diverse |pdf=|usr=}}{{40907998}} gab.com Text The spontaneous neoantigen-specific CD4(+) T-cell response to a growing tumor is functionally and phenotypically diverse JO: J Immunother Cancer http://www.kidney.de/pget.php?&tw=1&pmid=40907998 #FOAvip BACKGROUND: CD4(+) T cells play a critical role in the positive and negative regulation of cellular immunity through the many functional subsets they comprise. The progressive growth of immunogenic tumors which nonetheless generate mutation-specific T cells suggests that effective immune control may be avoided or suppressed at the level of the neoantigen-specific CD4(+) T-cell response. Despite their importance, little is known about the ontogeny, architecture, and development of the CD4(+) NeoAg-specific repertoire induced by progressively growing tumor. METHODS: We used a tetramer specific for a validated neoantigen, CTLC(H129>Q)/I-A(k), to characterize the ontogeny of natural CD4(+) T-cell responses to an aggressive and poorly immunogenic major histocompatibility complex class II-deficient tumor, squamous cell carcinoma VII (SCC VII), during progressive growth or following therapeutic peptide vaccination using a combination of flow cytometry, single-cell genomics, and T-cell receptor (TCR) gene engineering. RESULTS: We find that the natural CD4(+) T-cell response to a growing tumor is phenotypically and functionally diverse, with distinct subsets including type 1 helper, T follicular helper-like, and regulatory T cell (Treg) lineages appearing as early as 9 days after tumor implantation. Therapeutic vaccination using the CLTC(H129>Q) peptide in adjuvant plus alpha-programmed cell death protein-1 reduces the frequency of CLTC(H129>Q)-specific Treg in both tumor and tumor-draining lymph node. Single-cell transcriptomic analysis of CLTC-specific CD4(+) T cells recapitulated and extended the diversity of the response, with TCRs of varying affinity found within each functional subset. The TCR affinity differences did not strictly correlate with function, however, as even the lowest affinity TCRs isolated from Treg can mediate therapeutic efficacy against established tumors in the setting of adoptive cellular therapy (ACT). CONCLUSIONS: These findings offer unprecedented insight into the functional diversity of a natural neoantigen-specific CD4(+) T-cell response and show how immunotherapeutic intervention influences the phenotype, magnitude, and efficacy of the antitumor immune response. This information could lead to new approaches to immune monitoring in the clinical setting of checkpoint blockade immunotherapy and cancer vaccines. Furthermore, we show that Treg can be a potent source of TCRs that can mediate therapeutic benefit in the setting of ACT. Twit Text FOAVip The spontaneous neoantigen-specific CD4(+) T-cell response to a growing tumor is functionally and phenotypically diverse ????J Immunother Cancer http://www.kidney.de/pget.php?&tw=1&pmid=40907998 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=40907998 #FOAvip English Wikipedia <ref>{{Cite pmid|40907998}}</ref> The spontaneous neoantigen-specific CD4(+) T-cell response to a growing tumor is functionally and phenotypically diverse #MMPMID40907998 Griswold RQ; Brightman SE; Soria Zavala K; Ordaz-Arias MA; Djassemi N; Thota RR; Naradikian MS; Dose H; Alarcon S; Vijayanand P; Peters B; Miller AM; Cohen EEW; Schoenberger SP J Immunother Cancer 2025[Sep]; 13 (9): ä PMID40907998show ga BACKGROUND: CD4(+) T cells play a critical role in the positive and negative regulation of cellular immunity through the many functional subsets they comprise. The progressive growth of immunogenic tumors which nonetheless generate mutation-specific T cells suggests that effective immune control may be avoided or suppressed at the level of the neoantigen-specific CD4(+) T-cell response. Despite their importance, little is known about the ontogeny, architecture, and development of the CD4(+) NeoAg-specific repertoire induced by progressively growing tumor. METHODS: We used a tetramer specific for a validated neoantigen, CTLC(H129>Q)/I-A(k), to characterize the ontogeny of natural CD4(+) T-cell responses to an aggressive and poorly immunogenic major histocompatibility complex class II-deficient tumor, squamous cell carcinoma VII (SCC VII), during progressive growth or following therapeutic peptide vaccination using a combination of flow cytometry, single-cell genomics, and T-cell receptor (TCR) gene engineering. RESULTS: We find that the natural CD4(+) T-cell response to a growing tumor is phenotypically and functionally diverse, with distinct subsets including type 1 helper, T follicular helper-like, and regulatory T cell (Treg) lineages appearing as early as 9 days after tumor implantation. Therapeutic vaccination using the CLTC(H129>Q) peptide in adjuvant plus alpha-programmed cell death protein-1 reduces the frequency of CLTC(H129>Q)-specific Treg in both tumor and tumor-draining lymph node. Single-cell transcriptomic analysis of CLTC-specific CD4(+) T cells recapitulated and extended the diversity of the response, with TCRs of varying affinity found within each functional subset. The TCR affinity differences did not strictly correlate with function, however, as even the lowest affinity TCRs isolated from Treg can mediate therapeutic efficacy against established tumors in the setting of adoptive cellular therapy (ACT). CONCLUSIONS: These findings offer unprecedented insight into the functional diversity of a natural neoantigen-specific CD4(+) T-cell response and show how immunotherapeutic intervention influences the phenotype, magnitude, and efficacy of the antitumor immune response. This information could lead to new approaches to immune monitoring in the clinical setting of checkpoint blockade immunotherapy and cancer vaccines. Furthermore, we show that Treg can be a potent source of TCRs that can mediate therapeutic benefit in the setting of ACT. |*Antigens, Neoplasm/immunology[MESH] |*CD4-Positive T-Lymphocytes/immunology/metabolism[MESH] |Animals[MESH] |Humans[MESH] |Mice[MESH]The spontaneous neoantigen-specific CD4(+) T-cell response to a growin(epmc).pdf DeepDyve Pubget Overpricing