Iskanje po repozitoriju

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Povzetek: Various types of immunotherapy (i.e. immune checkpoint inhibitors [ICIs], chimeric antigen receptor [CAR] T-cells and bispecific T-cell engagers [BiTEs]) and antibody drug conjugates (ADCs) have been used increasingly to treat solid cancers, lymphomas and leukaemias. Patients with serious complications of these therapies can be presented to physicians of different specialties. In this narrative review we discuss potentially fatal complications of new systemic anticancer therapies and some practical considerations for their diagnosis and initial treatment. Results Clinical presentation of toxicities of new anticancer therapies may be unpredictable and nonspecific. They can mimic other more common medical conditions such as infection or stroke. If not recognized and properly treated these toxicities can progress rapidly into life-threatening conditions. ICIs can cause immune-related inflammatory disorders of various organ systems (e.g. pneumonitis or colitis), and a cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) may develop after treatment with CAR T-cells or BiTEs. The cornerstones of management of these hyper-inflammatory disorders are supportive care and systemic immunosuppressive therapy. The latter should start as soon as symptoms are mild-moderate. Similarly, some severe toxicities of ADCs also require immunosuppressive therapy. A multidisciplinary team including an oncologist/haematologist and a corresponding organ-site specialist (e.g. gastroenterologist in the case of colitis) should be involved in the diagnosis and treatment of these toxicities. Conclusions Health professionals should be aware of potential serious complications of new systemic anticancer therapies. Early diagnosis and treatment with adequate supportive care and immunosuppressive therapy are crucial for the optimal outcome of patients with these complications.
Ključne besede: potentially fatal toxicity, immune checkpoint inhibitors, immunosuppressive therapy
Objavljeno v DiRROS: 26.06.2026; Ogledov: 232; Prenosov: 87
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Ključne besede: immune checkpoint inhibitors, immune checkpoint inhibitors induced colitis, immune-mediated micro-scopic colitis, corticosteroid therapy, vedolizumab
Objavljeno v DiRROS: 24.06.2026; Ogledov: 199; Prenosov: 159
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Povzetek: Tumor-infiltrating lymphocytes (TILs) are an established predictor of pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) in breast cancer. However, TILs primarily reflect the extent of immune infiltration and provide limited insight into immune functional state. We investigated whether integrating measures of immune infiltration (TILs), effector T-cell presence (CD8), and functional context (immune checkpoint components) may improve prediction of pCR beyond TILs alone. Pretreatment tumor biopsies from 166 patients with early breast cancer treated with standard NACT were assessed for stromal TILs and mRNA expression of CD8, PD-1, LAG-3, and TIM-3. Associations with pCR were evaluated using univariate and multivariable logistic regression, and composite immune phenotypes were constructed to capture functional immune states. In univariate analyses, higher TILs, CD8, PD-1, and LAG-3 were associated with pCR (all p < 0.05), whereas TIM-3 was not (p = 0.801). In multivariable models, TILs remained independently associated with pCR when adjusted for checkpoint markers, but this association was attenuated when CD8 was included, consistent with the strong biological correlation between TILs and CD8, and neither CD8 nor checkpoint markers retained independent significance. PD-1 and LAG-3 expression strongly correlated with CD8 and moderately correlated with TILs, indicating that checkpoint expression predominantly reflects an immune effector-engaged tumor microenvironment. Composite immune phenotypes based on CD8/PD-1 co-expression identified distinct immune functional states, with CD8-high/PD-1-high tumors demonstrating the highest pCR rates. Hierarchical modeling showed modest improvements in discrimination with sequential addition of immune variables to clinical predictors, with the integrative CD8/PD-1 model achieving the highest discrimination within the cohort (AUC = 0.849), although the magnitude of improvement beyond TIL assessment alone was limited. In conclusion, immune infiltration, effector T-cell presence, and functional immune context represent complementary dimensions for pCR prediction following NACT in breast cancer. However, TILs remain the most robust and clinically feasible immune biomarker.
Ključne besede: PD-1 immune checkpoint, breast cancer, immune microenvironment, neoadjuvant chemotherapy
Objavljeno v DiRROS: 20.04.2026; Ogledov: 408; Prenosov: 308
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Povzetek: Background: Immunotherapy has been successful in treating advanced melanoma, but a large proportion of patients do not respond to the treatment with immune checkpoint inhibitors (ICIs). Preclinical and small cohort studies suggest gastrointestinal microbiome composition and exosomal mRNA expression of PD-L1 and IFNγ from the primary tumor, stool and body fluids as potential biomarkers for response. Methods: Patients treated with immune checkpoint inhibitors as a first line treatment for metastatic melanoma are recruted to this prospective study. Stool samples are submitted before the start of treatment, at the 12th (+/−2) week and 28th (+/−2) week, and at the occurrence of event (suspected disease progression/hyperprogression, immune-related adverse event (irAE), deterioration). Peripheral venous blood samples are taken additionally at the same time points for cytologic and molecular tests. Histological material from the tumor tissue is obtained before the start of immunotherapy treatment. Primary objectives are to determine whether the human gastrointestinal microbiome (bacterial and viral) and the exosomal mRNA expression of PD-L1 and IFNγ and its dynamics predicts the response to treatment with PD-1 and CTLA-4 inhibitors and its association with the occurrence of irAE. The response is evaluated radiologically with imaging methods in accordance with the irRECIST criteria. Conclusions: This is the first study to combine and investigate multiple potential predictive and prognostic biomarkers and their dynamics in first line ICI in metastatic melanoma patients.
Ključne besede: gastrointestinal microbiome, mRNA expression of PD-L1 and IFNγ, immune checkpoint inhibitors, metastatic melanoma
Objavljeno v DiRROS: 21.03.2024; Ogledov: 1835; Prenosov: 1104
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