RESUMO
Alveolar soft part sarcoma (ASPS) is a rare malignancy with low sensitivity to chemotherapy. While localized ASPS has a very good prognosis after resection, the 5-year overall survival rate drops substantially in metastatic disease. We report the case of an 80-year-old male patient with ASPS of the left elbow and metastasis to the lung, lymph nodes and peritoneum. After weighing the benefits and risks, systemic treatment with the anti-PD-1 checkpoint inhibitor pembrolizumab combined with the vascular endothelial growth factor receptor tyrosinkinase inhibitor axitinib was initiated in this patient with a history of psoriasis and Crohn's disease. After only two cycles of therapy, a significant size reduction of the nodal cervical metastasis became apparent. A partial response of all metastases was then confirmed in the first computed tomography restaging. So far, side effects have remained manageable, especially with regard to the development or worsening of autoimmune adverse events. The patient continued to have a high quality of life, while also remaining in ongoing partial response for 15 months at the time of submission. While sarcomas generally have low sensitivity to immunotherapies, ASPS is an exception, and checkpoint inhibition is an integral part of its systemic therapy.
Assuntos
Doenças Autoimunes , Sarcoma Alveolar de Partes Moles , Masculino , Humanos , Idoso de 80 Anos ou mais , Axitinibe/uso terapêutico , Sarcoma Alveolar de Partes Moles/tratamento farmacológico , Sarcoma Alveolar de Partes Moles/patologia , Sarcoma Alveolar de Partes Moles/cirurgia , Qualidade de Vida , Fator A de Crescimento do Endotélio Vascular , Inibidores da Angiogênese/uso terapêutico , Doenças Autoimunes/tratamento farmacológicoRESUMO
For decades, treatment of advanced biliary tract cancer (BTC) was confined to the use of chemotherapy. In recent years however, the number of therapeutic options available for patients with unresectable BTC have drastically increased, with immunotherapy and targeted treatment gradually joining the ranks of guideline-recommended treatment regimens. The aim of the present review is to summarise the current knowledge on unresectable BTC focusing on epidemiology, anatomical distribution and current strategies for systemic treatment. We further outline ongoing clinical trials and provide an outlook on future therapeutic interventions. In the realm of gastrointestinal malignancies, the increasing number of systemic treatment options for BTC is finally delivering on the longstanding commitment to personalised oncology. This emphasises the need for considering a comprehensive genomic-based pathology assessment right from the initial diagnosis to fully leverage the expanding array of therapeutic options that have recently become accessible.
Assuntos
Neoplasias do Sistema Biliar , Humanos , Neoplasias do Sistema Biliar/terapia , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/patologia , Imunoterapia/métodos , Terapia de Alvo Molecular/métodosRESUMO
PURPOSE: The combination of gemcitabine/nab-paclitaxel is an established standard treatment in the first-line treatment of metastatic ductal adenocarcinoma of the pancreas (mPDAC). Afatinib, an oral second-generation pan ErbB family tyrosine kinase inhibitor, has shown promising pre-clinical signs in the treatment of pancreatic cancer. The aim of this phase 1b trial was to determine the maximum tolerated dose (MTD) of afatinib in combination with gemcitabine/nab-paclitaxel in patients with mPDAC. METHODS: Treatment naïve patients (≥18 years) with histologically proven mPDAC and good performance status (ECOG 0/1) were enrolled to receive gemcitabine/nab-paclitaxel in combination with afatinib. Treatment was continued until disease progression, or unacceptable toxicity. The primary endpoint MTD was determined using a 3 + 3 design. Treatment started at dose level 0 with intravenous gemcitabine/nab-paclitaxel 1000 mg/m2 / 125 mg/m2 (day 1, 8, 15 of a 28-day cycle) + oral afatinib 30 mg daily. At dose level + 1 afatinib was increased to 40 mg. Secondary endpoints included safety parameters and exploratory endpoints evaluated treatment efficacy. RESULTS: Twelve patients were included in this trial, and 11 patients were treated and analysed in the safety and full analysis set (FAS). At dose level 0 the first three patients did not experience a dose-limiting toxicity (DLT). At dose leve (DL) + 1 two patients experienced a DLT. Accordingly, enrolment continued at DL 0 with three more patients, of which one experienced DLT (skin rash ≥ CTCAE grade 3). Seven patients (63.6%) experienced at least one treatment-emergent serious adverse event (TESAE), with four patients (36.4%) experiencing TESAEs grade 3-5 related to the study medication. In the FAS, the objective response rate (ORR) was 36.4%, median progression-free survival (PFS) was 3.5 months and median overall survival in nine evaluable patients was 7.5 months. CONCLUSIONS: In this phase 1b clinical trial, the MTD of gemcitabine/nab-paclitaxel (1000 mg/m2 / 125 mg/m2) and afatinib (30 mg) was established. In a cohort of 11 patients, the combination showed an acceptable safety profile.
Assuntos
Gencitabina , Neoplasias Pancreáticas , Humanos , Afatinib/efeitos adversos , Desoxicitidina , Paclitaxel , Albuminas , Neoplasias Pancreáticas/patologia , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
PURPOSE: To analyze the 3-month life expectancy rate in pancreatic cancer (PC) patients treated within prospective trials from the German AIO study group. PATIENTS AND METHODS: A pooled analysis was conducted for patients with advanced PC that were treated within five phase II/III studies conducted between 1997 and 2017 (Gem/Cis, Ro96, RC57, ACCEPT, RASH). The primary goal for the current report was to identify the actual 3-month survival rate, a standard inclusion criterion in oncology trials. RESULTS: Overall, 912 patients were included, 83% had metastatic and 17% locally advanced PC; the estimated median overall survival (OS) was 7.1 months. Twenty-one percent of the participants survived < 3 months, with a range from 26% in RC57 to 15% in RASH. Significant predictors for not reaching 3-month OS were > 1 previous treatment line (p < 0.001) and performance status (p < 0.001). CONCLUSIONS: Despite the definition of a life expectancy of > 3 months as a standard inclusion criterion in clinical trials for advanced PC, a significant proportion of study patients does not survive > 3 months. TRIAL REGISTRATION NUMBERS: NCT00440167 (AIO-PK0104), NCT01729481 (RASH), NCT01728818 (ACCEPT).
RESUMO
BACKGROUND: A standardised dose-reduction strategy has not been established for the widely used gemcitabine plus nab-paclitaxel regimen in patients with metastatic pancreatic ductal adenocarcinoma. We aimed to investigate the efficacy and tolerability of alternating treatment cycles of nab-paclitaxel-gemcitabine combination therapy and gemcitabine alone versus continuous treatment with the nab-paclitaxel-gemcitabine combination. METHODS: ALPACA was a randomised, open-label, phase 2 trial conducted at 29 study centres across Germany. Patients aged 18 years or older with a histologically or cytologically confirmed diagnosis of metastatic pancreatic ductal adenocarcinoma who had not been previously treated for advanced disease were enrolled. After an induction phase with three cycles of nab-paclitaxel-gemcitabine combination therapy (nab-paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2 administered intravenously on days 1, 8, and 15 of each 28-day cycle), patients were randomly assigned (1:1) by stratified permuted block randomisation either to continue treatment with standard nab-paclitaxel-gemcitabine or to receive alternating cycles of nab-paclitaxel-gemcitabine and gemcitabine alone. Patients and investigators were not masked to treatment allocation. Randomisation was done centrally by the study statistician using a computer-generated randomisation list, and was stratified by Karnofsky Performance Status and presence of liver metastases. The primary endpoint was the derivation of an unbiased point estimate and an associated confidence interval with a confidence coefficient of 80% for the hazard ratio (HR) for overall survival after randomisation, without testing a specific hypothesis, analysed by intention to treat in all patients who started randomised treatment. Safety was analysed according to treatment received. This trial is registered with ClinicalTrials.gov, NCT02564146, and is completed. FINDINGS: Between May 27, 2016, and May 27, 2021, 325 patients were enrolled. Following three cycles of induction treatment, 174 patients were randomly assigned: 85 to continue receiving standard nab-paclitaxel-gemcitabine, of whom 79 started treatment, and 89 to the alternating treatment schedule, of whom 88 started treatment. Of the 167 patients who started randomised treatment, 88 (53%) were female and 79 (47%) were male. Median overall survival after randomisation was 10·4 months (80% CI 9·2-12·0) in the group that received standard treatment and 10·5 months (10·2-11·1) in the group that received alternating treatment (HR 0·90, 80% CI 0·72-1·13; p=0·56). The most common adverse events of any grade were peripheral neuropathy (59 [74%] of 80 patients in the continuous treatment group vs 53 [62%] of 85 patients in the alternating treatment group) and fatigue (43 [54%] vs 44 [52%]). Treatment-emergent serious adverse events after randomisation occurred in 40 (50%) patients in the continuous treatment group and in 28 (33%) in the alternating treatment group. Fewer treatment-emergent adverse events of grade 3 or higher occurred in patients treated with alternating cycles compared with those receiving standard therapy, especially for peripheral neuropathy (17 [21%] patients in the continuous treatment group vs 12 [14%] in the alternating treatment group) and infections (16 [20%] vs nine [11%]). There were two treatment-related deaths after randomisation, both in the continuous treatment group (one multiple organ dysfunction syndrome, not treated after randomisation, and one interstitial lung disease). INTERPRETATION: Our findings suggest that a dose-reduced regimen with alternating cycles of nab-paclitaxel-gemcitabine and gemcitabine alone after three induction cycles is associated with similar overall survival to that for standard treatment with nab-paclitaxel-gemcitabine, but with improved tolerability. We therefore propose that a switch to the alternating schedule could be considered in a clinical setting for patients with metastatic pancreatic cancer who have at least stable disease after three cycles of nab-paclitaxel-gemcitabine treatment. FUNDING: Celgene/Bristol Myers Squibb.
RESUMO
BACKGROUND/AIM: Endometriosis is a common disorder in reproductive-age women leading to a broad range of symptoms and is associated with a higher risk for endometrioid ovarian carcinoma. CASE REPORT: We report the case of a 55 year-old woman with previously undiagnosed endometriosis presenting with a large mediastinal cancer of unknown primary (CUP) and synchronous Union Internationale Contre le Cancer (UICC) stage II rectal adenocarcinoma. Histopathologically the mediastinal tumor resembled endometrial carcinoma and laparoscopically endometriotic lesions on the patient's peritoneum were detected. The patient was treated with neoadjuvant carboplatin and paclitaxel, followed by resection of the mediastinal tumor. After recovery, the patient received neoadjuvant short-course radiation to the rectal adenocarcinoma, which was resected afterwards. No primary endometrial carcinoma was found in the uterus, leading to the most likely conclusion that the mediastinal tumor derived from an extragenital endometriotic lesion. CONCLUSION: Although rare, cases of degeneration of endometriosis have been described. In this case not only the localization of endometriosis was uncommon, but also its malignant transformation and synchronous diagnosis of a rectal adenocarcinoma, complicating diagnosis, and treatment of the patient. This rare case highlights the importance of diagnosing and treating patients with CUP or multiple malignancies at large interdisciplinary centers to reach the best possible outcome.
Assuntos
Carcinoma Endometrioide , Neoplasias do Endométrio , Endometriose , Neoplasias do Mediastino , Neoplasias Retais , Humanos , Feminino , Pessoa de Meia-Idade , Endometriose/complicações , Endometriose/patologia , Neoplasias do Endométrio/patologia , Carcinoma Endometrioide/patologia , Neoplasias Retais/complicações , Neoplasias Retais/terapiaRESUMO
INTRODUCTION: To this date, surgery remains the only potentially curative approach in the treatment of pancreatic cancer. To analyse the clinical impact of a structured post-operative follow-up programme, we retrospectively analysed a cohort of resected pancreatic adenocarcinoma patients treated at LMU Munich. METHODS: Pancreatic adenocarcinoma patients who underwent resection and presented for regular follow-up visits at our centre between 2002 and 2017 were identified from two existing study cohorts. Diagnosis of recurrences was categorised by timing (within or outside a scheduled follow-up visit) and detection modality (imaging, CA 19-9 increase, or clinical deterioration) and correlated with disease-free survival and overall survival (OS). RESULTS: One hundred and twenty-five patients with resected pancreatic adenocarcinoma were included in this analysis. Median OS in the whole cohort was 21.1 months. Of these 125 patients, 103 (82.4%) patients had a documented relapse. Tumour recurrences detected within a scheduled follow-up visit (n = 86, 83.5%) compared to recurrences becoming apparent at an unplanned visit (n = 17, 16.5%) were associated with a significantly improved OS (median 25.5 vs. 20.2 months, p = 0.019). Compared to patients with recurrence detected by clinical deterioration (n = 4, 3.9%), patients with recurrences detected by imaging or laboratory abnormalities (n = 99, 96.0%) had a longer median OS (24.8 vs. 15.1 months, p = 0.007). DISCUSSION: A structured follow-up after pancreatic ductal adenocarcinoma resection may have an impact on patient outcome. Prospective trials are needed to evaluate the clinical impact of post-operative follow-up programmes.
Assuntos
Adenocarcinoma , Carcinoma Ductal Pancreático , Deterioração Clínica , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Estudos Retrospectivos , Adenocarcinoma/patologia , Estudos Prospectivos , Recidiva Local de Neoplasia , Carcinoma Ductal Pancreático/patologia , Seguimentos , Neoplasias PancreáticasRESUMO
PURPOSE: Novel biomarkers to better predict outcome and select the best therapeutic strategy for the individual patient are necessary for pancreatic ductal adenocarcinoma (PDAC). METHODS: Using a panel assay, multiple biomarkers (IFN-γ, IL-10, IL-6, IL-8, TNF-α, CEA, CA 19-9, CYFRA 21-1, HE4, PD-1 and PD-L1 levels) were measured in serum samples of 162 patients with resected, locally advanced and metastatic PDAC in this retrospective single-center study. Optimal cut-off values to differentiate prognostic subgroups with significantly different overall survival (OS) were determined by receiver operator characteristics and Youden Index analysis. Marker levels were assessed before the start of chemotherapy and correlated with OS by univariate and multivariate Cox analysis. RESULTS: Median OS for resected patients was 28.2 months, for locally advanced patients 17.9 months and for patients with metastatic disease 8.6 months. CYFRA 21-1 and IL-8 discriminated metastatic from locally advanced patients best (AUC 0.85 and AUC 0.81, respectively). In univariate analyses, multiple markers showed prognostic relevance in the various subgroups. However, multivariate Cox models comprised only CYFRA 21-1 in the resected group (HR 1.37, p = 0.015), IL-10 in locally advanced PDAC (HR 10.01, p = 0.014), as well as CYFRA 21-1 and CA 19-9 in metastatic PDAC (p = 0.008 and p = 0.010) as an independent prognostic marker for overall survival. CONCLUSION: IL-10 levels may have independent prognostic value in locally advanced PDAC, whereas CYFRA 21-1 levels are prognostic after PDAC surgery. CYFRA 21-1 and IL-8 have been identified to best discriminate metastatic from locally advanced patients.
Assuntos
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Biomarcadores Tumorais , Interleucina-10 , Fator de Necrose Tumoral alfa/uso terapêutico , Receptor de Morte Celular Programada 1 , Antígeno B7-H1 , Estudos Retrospectivos , Interleucina-8 , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Prognóstico , Adenocarcinoma/patologia , Neoplasias PancreáticasRESUMO
BACKGROUND: In pancreatic cancer, systemic treatment options in addition to chemotherapy remain scarce, and so far only a small proportion of patients benefit from targeted therapies. OBJECTIVE: The patients with pancreatic cancer discussed in the CCCMunichLMU Molecular Tumor Board were reviewed to gain a better real-world understanding of the challenges and chances of precision oncology in this hard-to-treat cancer. METHODS: Patients with pancreatic cancer who received comprehensive genomic profiling and were discussed in the interdisciplinary Molecular Tumor Board between May 2017 and July 2022 were included. These patients' medical charts, comprehensive genomic profiling results, and Molecular Tumor Board recommendations were analyzed in this retrospective cohort study. RESULTS: Molecular profiles of 165 patients with pancreatic cancer were discussed in the Molecular Tumor Board. In the 149 cases where comprehensive genomic profiling was successful, KRAS mutations were detected in 87.9%, TP53 in 53.0%, and CDKN2A in 14.1%. 33.3% of KRAS wild-type patients harbored targetable mutations, while these were only found in 19.1% of patients with the KRAS mutation; however, this difference was not statistically significant. 63.8% of patients with successful testing received a targeted treatment recommendation by the Molecular Tumor Board; however, only 3.2% of these were put into practice. Compared to a historic cohort of patients with pancreatic cancer with synchronous metastatic disease diagnosed between 2010 and 2017, the patients from the pancreatic cancer cohort with synchronous metastatic disease had a longer survival. CONCLUSIONS: This single-center experience emphasizes the challenges of targeted treatment in pancreatic cancer. Very few patients ultimately received the recommended therapies, highlighting the need for more and better targeted treatment options in pancreatic cancer, early comprehensive genomic profiling to allow sufficient time to put Molecular Tumor Board recommendations into practice, and close cooperation with clinical trial units to give patients access to otherwise not available targeted treatments.
Assuntos
Neoplasias Pancreáticas , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Estudos Retrospectivos , Proteínas Proto-Oncogênicas p21(ras)/genética , Medicina de Precisão/métodos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/tratamento farmacológico , Mutação , Terapia de Alvo Molecular/métodos , Neoplasias PancreáticasRESUMO
This analysis of the RASH trial (NCT01729481) aimed at gaining a better understanding of the "Burden of Therapy" (BOTh®TM) in pancreatic ductal adenocarcinoma (PDAC). In the RASH study, 150 patients with newly diagnosed metastatic PDAC were treated with gemcitabine plus erlotinib (gem/erlotinib) for four weeks. Patients who developed a skin rash during this four-week run-in phase continued with the gem/erlotinib treatment, while rash-negative patients were switched to FOLFIRINOX. The study demonstrated a 1-year survival rate of rash-positive patients who received gem/erlotinib as first-line treatment that was comparable to previous reports of patients receiving FOLFIRINOX. To understand whether these comparable survival rates may be accompanied by better tolerability of the gem/erlotinib treatment compared to FOLFIRINOX, the BOTh®TM methodology was used to continuously quantify and depict the burden of therapy generated by treatment emergent events (TEAEs). Sensory neuropathy was significantly more common in the FOLFIRINOX arm, and prevalence as well as severity increased over time. In both arms, the BOTh®TM associated with diarrhea decreased over the course of treatment. The BOTh®TM caused by neutropenia was comparable in both arms but decreased in the FOLFIRINOX arm over time, possibly due to chemotherapy dose reductions. Overall, gem/erlotinib was associated with a slightly higher overall BOTh®TM, but the difference was not statistically significant (p = 0.6735). In summary, the BOTh®TM analysis facilitates the evaluation of TEAEs. In patients fit for intense chemotherapeutic regimens, FOLFIRINOX is associated with a lower BOTh®TM than gem/erlotinib.
Assuntos
Exantema , Neoplasias Pancreáticas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cloridrato de Erlotinib/efeitos adversos , Exantema/induzido quimicamente , Exantema/tratamento farmacológico , Ensaios Clínicos como Assunto , Neoplasias PancreáticasRESUMO
BACKGROUND AND OBJECTIVE: With the rising importance of precision oncology in biliary tract cancer (BTC), the aim of this retrospective single-center analysis was to describe the clinical and molecular characteristics of patients with BTC who underwent comprehensive genomic profiling (CGP) and were discussed in the CCCMunichLMU molecular tumor board (MTB). PATIENTS AND METHODS: In this single-center observational study, we included BTC patients with intrahepatic cholangiocarcinoma (iCCA), extrahepatic CCA (eCCA), and gallbladder cancer (GB), who had been discussed in the institutional MTB from May 29, 2017, to July 25, 2022. Patients were followed up until 31 January 2023. Data were retrospectively collected by review of medical charts, and MTB recommendation. RESULTS: In total, 153 cases were registered to the MTB with a median follow-up of 15 months. Testing was successful in 81.7% of the patients. CGP detected targetable alterations in 35.3% of our BTC patients (most commonly ARID1A/ERBB2/IDH1/PIK3CA/BRAF-mutations and FGFR2-fusions). Recommendations for molecularly guided therapy were given in 46.4%. Of those, treatment implementation of targeted therapy followed in 19.4%. In patients receiving the recommended treatment, response rate was 57% and median overall survival was 19 months (vs 8 months in the untreated cohort). The progression-free survival ratio of 1.45 suggest a clinical benefit of molecularly guided treatment. CONCLUSIONS: In line with previous work, our series demonstrates feasibility and clinical utility of comprehensive genomic profiling in BTC patients. With the growing number of targeted agents with clinical activity in BTC, CGP should become standard of care in the management of this group of patients.
Assuntos
Neoplasias dos Ductos Biliares , Neoplasias do Sistema Biliar , Humanos , Estudos Retrospectivos , Medicina de Precisão , Neoplasias do Sistema Biliar/genética , Neoplasias do Sistema Biliar/terapia , Neoplasias do Sistema Biliar/patologia , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologiaRESUMO
INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) has a 5-year overall survival rate of 10%, emphasizing the need for more effective therapies, especially in metastatic disease. The immunosuppressive tumor microenvironment, poor vascularization, and dense tumor stroma typical for PDAC are hurdles that need to be overcome by novel drugs. Investigations are moving toward more targeted treatments including immunotherapy and cell-based approaches. AREAS COVERED: This article reviews emerging drugs in clinical development for metastatic PDAC, focusing on cellular therapies and novel treatments targeting metabolism, tumor stroma, oncogenic pathways and immunosuppression. With immunotherapy and CAR T-cell therapy on the rise in hematological malignancies, the transfer to solid tumors remains intriguing. Multiple exciting clinical trials investigating innovative therapeutic strategies for PDAC are currently ongoing and reviewed herein. ClinicalTrials.gov, conference abstracts and PubMed were searched in August 2021 and assessed for information on ongoing and published clinical studies. EXPERT OPINION: With many challenges to overcome, the optimal therapy for patients with metastatic PDAC is likely to consist of a combination of different agents. We are slowly moving from entity-dependent approaches to ones more focused on molecular and pathological features. Increasingly personalized treatment plans tailored to each patient may be the future of PDAC therapy.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Humanos , Imunoterapia , Terapia de Alvo Molecular , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Microambiente TumoralRESUMO
CAR T cell therapy remains ineffective in solid tumors, due largely to poor infiltration and T cell suppression at the tumor site. T regulatory (Treg) cells suppress the immune response via inhibitory factors such as transforming growth factor-ß (TGF-ß). Treg cells expressing the C-C chemokine receptor 8 (CCR8) have been associated with poor prognosis in solid tumors. We postulated that CCR8 could be exploited to redirect effector T cells to the tumor site while a dominant-negative TGF-ß receptor 2 (DNR) can simultaneously shield them from TGF-ß. We identified that CCL1 from activated T cells potentiates a feedback loop for CCR8+ T cell recruitment to the tumor site. This sustained and improved infiltration of engineered T cells synergized with TGF-ß shielding for improved therapeutic efficacy. Our results demonstrate that addition of CCR8 and DNR into CAR T cells can render them effective in solid tumors.
Assuntos
Neoplasias , Humanos , Neoplasias/terapia , Linfócitos T Reguladores , Fator de Crescimento Transformador beta/farmacologiaRESUMO
The efficacy of adoptive cell therapy for solid tumours is hampered by the poor accumulation of the transferred T cells in tumour tissue. Here, we show that forced expression of C-X-C chemokine receptor type 6 (whose ligand is highly expressed by human and murine pancreatic cancer cells and tumour-infiltrating immune cells) in antigen-specific T cells enhanced the recognition and lysis of pancreatic cancer cells and the efficacy of adoptive cell therapy for pancreatic cancer. In mice with subcutaneous pancreatic tumours treated with T cells with either a transgenic T-cell receptor or a murine chimeric antigen receptor targeting the tumour-associated antigen epithelial cell adhesion molecule, and in mice with orthotopic pancreatic tumours or patient-derived xenografts treated with T cells expressing a chimeric antigen receptor targeting mesothelin, the T cells exhibited enhanced intratumoral accumulation, exerted sustained anti-tumoral activity and prolonged animal survival only when co-expressing C-X-C chemokine receptor type 6. Arming tumour-specific T cells with tumour-specific chemokine receptors may represent a promising strategy for the realization of adoptive cell therapy for solid tumours.