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1.
Nat Commun ; 15(1): 1585, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383563

RESUMO

Dynamic interactions within the tumor micro-environment drive patient response to immune checkpoint inhibitors. Existing preclinical models lack true representation of this complexity. Using a Head and Neck cancer patient derived TruTumor histoculture platform, the response spectrum of 70 patients to anti-PD1 treatment is investigated in this study. With a subset of 55 patient samples, multiple assays to characterize T-cell reinvigoration and tumor cytotoxicity are performed. Based on levels of these two response parameters, patients are stratified into five sub-cohorts, with the best responder and non-responder sub-cohorts falling at extreme ends of the spectrum. The responder sub-cohort exhibits high T-cell reinvigoration, high tumor cytotoxicity with T-cells homing into the tumor upon treatment whereas immune suppression and tumor progression pathways are pre-dominant in the non-responders. Some moderate responders benefit from combination of anti-CTLA4 with anti-PD1, which is evident from better cytotoxic T-cell: T-regulatory cell ratio and enhancement of tumor cytotoxicity. Baseline and on-treatment gene expression signatures from this study stratify responders and non-responders in unrelated clinical datasets.


Assuntos
Neoplasias de Cabeça e Pescoço , Humanos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Microambiente Tumoral
2.
Cureus ; 13(7): e16389, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34408942

RESUMO

Mean platelet volume (MPV) is an inflammatory marker indicative of platelet activation. There are several studies that suggest an association between the neoplastic process and cancer metastasis. We performed a retrospective analysis to investigate the role of MPV as a prognostic informative marker in gallbladder cancer. This study included 73 patients who underwent treatment for gallbladder cancer with curative or palliative intent. MPV was obtained and statistically analysed to investigate the association between the nodal status (N), the overall stage as per the American Joint Committee on Cancer (AJCC) staging system, perineural invasion, and differentiation of the tumor. The statistical analysis was done using SPSS Statistics, version 23 (IBM Corp., Armonk, NY). We found that the MPV values were significantly high in node-positive cases (OR = 3.623, 95% CI = 7.778-1.687, p value = -0.0001), cases in the advanced stage (OR = 3.623, 95% CI = 7.778-1.687, p value = 0.0001), cases with perineural invasion (OR = 3.396, 95% CI = 8.319-1.387, p value = -0.0001), and poor differentiation (OR = 2.327, 95% CI = 4.651-1.164, p value = -0.002 ). MPV is an inexpensive and convenient inflammatory marker that correlates with nodal positivity in the staging and prognostication of gallbladder cancer. This marker can be used to ascertain the risk status of gallbladder cancer.

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