Ramya Muddasani, Neel Talwar, Isa Mambetsariev, Jeremy Fricke, Mercury Lin, Daniel Schmolze, Andrew Yue, Amna Rizvi, Ravi Salgia
{"title":"Clinical features associated with immune checkpoint inhibitor nephritis: a single-center clinical case series.","authors":"Ramya Muddasani, Neel Talwar, Isa Mambetsariev, Jeremy Fricke, Mercury Lin, Daniel Schmolze, Andrew Yue, Amna Rizvi, Ravi Salgia","doi":"10.1007/s00262-024-03775-6","DOIUrl":"10.1007/s00262-024-03775-6","url":null,"abstract":"<p><strong>Background: </strong>Acute kidney injury (AKI) has been well described as a complication of immune checkpoint inhibitor therapy. We present a series of patients, the majority with lung adenocarcinoma, who developed AKI while actively receiving immune checkpoint inhibitors.</p><p><strong>Methods: </strong>This is a retrospectively analyzed clinical case series of six patients treated at City of Hope Comprehensive Cancer Center. Data were collected on gender, age, ethnicity, comorbidities, concomitant medications, type of malignancy, treatments, and renal function. All patients underwent renal biopsy for classification of the mechanism of AKI. Comprehensive genomic profiling (CGP) was performed on tumor tissue for all patients.</p><p><strong>Results: </strong>Patterns of AKI included acute interstitial nephritis and acute tubular necrosis. Contributing factors included the use of concomitant medications known to contribute to AKI. All but two patients had full resolution of the AKI with the use of steroids. There were several mutations found on CGP that was notable including an Exon 20 insertion as well as multiple NF1 and TP53 mutations. There was high PD-L1 expression on tumor tissue noted in two out of six patients. In addition to AKI, a subset of patients had proteinuria with biopsies revealing corresponding glomerular lesions of minimal change disease and focal and segmental glomerulosclerosis.</p><p><strong>Conclusions: </strong>Our case series demonstrates that AKI from immune checkpoint inhibitors has a variable presentation that may require an individualized treatment approach. Further studies are needed to identify biomarkers that may help identify those at risk and guide the management of this condition.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 10","pages":"200"},"PeriodicalIF":4.6,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Qin Wang, Fan Tong, Li Qiao, Liang Qi, Yi Sun, Yahui Zhu, Jiayao Ni, Juan Liu, Weiwei Kong, Baorui Liu, Juan Du
{"title":"Hypofractionated radiotherapy plus PD-1 antibody and SOX chemotherapy as second-line therapy in metastatic pancreatic cancer: a single-arm, phase II clinical trial.","authors":"Qin Wang, Fan Tong, Li Qiao, Liang Qi, Yi Sun, Yahui Zhu, Jiayao Ni, Juan Liu, Weiwei Kong, Baorui Liu, Juan Du","doi":"10.1007/s00262-024-03744-z","DOIUrl":"10.1007/s00262-024-03744-z","url":null,"abstract":"<p><strong>Purpose: </strong>To assess the efficacy and safety of concurrent hypofractionated radiotherapy plus anti-PD-1 antibody and SOX chemotherapy in the treatment of metastatic pancreatic cancer (mPC) after failure of first-line chemotherapy.</p><p><strong>Methods: </strong>Patients with pathologically confirmed mPC who failed standard first-line chemotherapy were enrolled. The patients were treated with a regimen of hypofractionated radiotherapy, SOX chemotherapy, and immune checkpoint inhibitors at our institution. We collected the patients' clinical information and outcome measurements. The median progression-free survival (mPFS) was the primary endpoint of the study, followed by disease control rate (DCR), objective response rate (ORR), median overall survival (mOS) and safety. Exploratory analyses included biomarkers related to the benefits.</p><p><strong>Results: </strong>Between February 24, 2021, and August 30, 2023, twenty-five patients were enrolled in the study, and twenty-three patients who received at least one dose of the study agent had objective efficacy evaluation. The mPFS was 5.48 months, the mOS was 6.57 months, and the DCR and ORR were 69.5% and 30.4%, respectively. Among the seven patients who achieved a PR, the median duration of the response was 7.41 months. On-treatment decreased serum CA19-9 levels were associated with better overall survival. Besides, pretreatment inflammatory markers were associated with tumor response and survival.</p><p><strong>Conclusions: </strong>Clinically meaningful antitumor activity and favorable safety profiles were demonstrated after treatment with these combination therapies in patients with refractory mPC. On-treatment decreased serum CA19-9 levels and pretreatment inflammatory markers platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), lactate dehydrogenase (LDH) might be biomarkers related to clinical benefits.</p><p><strong>Clinical trial registration: </strong>https://www.chictr.org.cn/showproj.html?proj=130211 , identifier: ChiCTR2100049799, date of registration: 2021-08-09.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 10","pages":"201"},"PeriodicalIF":4.6,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303639/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ravit Geva, Maria Vieito, Jorge Ramon, Ruth Perets, Manuel Pedregal, Elena Corral, Bernard Doger, Emiliano Calvo, Jorge Bardina, Elena Garralda, Regina J Brown, James G Greger, Shujian Wu, Douglas Steinbach, Tsun-Wen Sheena Yao, Yu Cao, Josh Lauring, Ruchi Chaudhary, Jaymala Patel, Bharvin Patel, Victor Moreno
{"title":"Safety and clinical activity of JNJ-78306358, a human leukocyte antigen-G (HLA-G) x CD3 bispecific antibody, for the treatment of advanced stage solid tumors.","authors":"Ravit Geva, Maria Vieito, Jorge Ramon, Ruth Perets, Manuel Pedregal, Elena Corral, Bernard Doger, Emiliano Calvo, Jorge Bardina, Elena Garralda, Regina J Brown, James G Greger, Shujian Wu, Douglas Steinbach, Tsun-Wen Sheena Yao, Yu Cao, Josh Lauring, Ruchi Chaudhary, Jaymala Patel, Bharvin Patel, Victor Moreno","doi":"10.1007/s00262-024-03790-7","DOIUrl":"10.1007/s00262-024-03790-7","url":null,"abstract":"<p><strong>Background: </strong>JNJ-78306358 is a bispecific antibody that redirects T cells to kill human leukocyte antigen-G (HLA-G)-expressing tumor cells. This dose escalation study evaluated the safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of JNJ-78306358 in patients with advanced solid tumors.</p><p><strong>Methods: </strong>Adult patients with metastatic/unresectable solid tumors with high prevalence of HLA-G expression were enrolled. Dose escalation was initiated with once-weekly subcutaneous administration with step-up dosing to mitigate cytokine release syndrome (CRS).</p><p><strong>Results: </strong>Overall, 39 heavily pretreated patients (colorectal cancer: n = 23, ovarian cancer: n = 10, and renal cell carcinoma: n = 6) were dosed in 7 cohorts. Most patients (94.9%) experienced ≥ 1 treatment-emergent adverse events (TEAEs); 87.2% had ≥ 1 related TEAEs. About half of the patients (48.7%) experienced CRS, which were grade 1/2. Nine patients (23.1%) received tocilizumab for CRS. No grade 3 CRS was observed. Dose-limiting toxicities (DLTs) of increased transaminases, pneumonitis and recurrent CRS requiring a dose reduction were reported in 4 patients, coinciding with CRS. No treatment-related deaths reported. No objective responses were noted, but 2 patients had stable disease > 40 weeks. JNJ-78306358 stimulated peripheral T cell activation and cytokine release. Anti-drug antibodies were observed in 45% of evaluable patients with impact on exposure. Approximately half of archival tumor samples (48%) had expression of HLA-G by immunohistochemistry.</p><p><strong>Conclusion: </strong>JNJ-78306358 showed pharmacodynamic effects with induction of cytokines and T cell activation. JNJ-78306358 was associated with CRS-related toxicities including increased transaminases and pneumonitis which limited its dose escalation to potentially efficacious levels. Trial registration number ClinicalTrials.gov (No. NCT04991740).</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 10","pages":"205"},"PeriodicalIF":4.6,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jacqueline E Mann, Nitzan Hasson, David G Su, Adebowale J Adeniran, Keiran S M Smalley, Dijana Djureinovic, Lucia B Jilaveanu, David A Schoenfeld, Harriet M Kluger
{"title":"GP100 expression is variable in intensity in melanoma.","authors":"Jacqueline E Mann, Nitzan Hasson, David G Su, Adebowale J Adeniran, Keiran S M Smalley, Dijana Djureinovic, Lucia B Jilaveanu, David A Schoenfeld, Harriet M Kluger","doi":"10.1007/s00262-024-03776-5","DOIUrl":"10.1007/s00262-024-03776-5","url":null,"abstract":"<p><p>Drugs or cellular products that bind to gp100 are being investigated for treatment of cutaneous melanoma. The relative specificity of gp100 expression in melanocytes makes it an attractive target to harness for therapeutic intent. For example, Tebentafusp, a bispecific gp100 peptide-HLA-directed CD3 T cell engager, has generated significant enthusiasm in recent years due to its success in improving outcomes for uveal melanoma and is being studied in cutaneous melanoma. However, the extent and intensity of gp100 expression in advanced cutaneous melanoma has not been well studied. Here, we interrogated a large cohort of primary and metastatic melanomas for gp100 expression by immunohistochemistry. Expression in metastatic samples was globally higher and almost uniformly positive, however the degree of intensity was variable. Using a quantitative immunofluorescence method, we confirmed the variability in expression. As gp100-binding drugs are assessed in clinical trials, the association between activity of the drugs and the level of gp100 expression should be studied in order to potentially improve patient selection.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 10","pages":"191"},"PeriodicalIF":4.6,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oscar Perales, Lucia Jilaveanu, Adebowale Adeniran, David G Su, Michael Hurwitz, David A Braun, Harriet M Kluger, David A Schoenfeld
{"title":"TIGIT expression in renal cell carcinoma infiltrating T cells is variable and inversely correlated with PD-1 and LAG3.","authors":"Oscar Perales, Lucia Jilaveanu, Adebowale Adeniran, David G Su, Michael Hurwitz, David A Braun, Harriet M Kluger, David A Schoenfeld","doi":"10.1007/s00262-024-03773-8","DOIUrl":"10.1007/s00262-024-03773-8","url":null,"abstract":"<p><strong>Purpose: </strong>Immune checkpoint inhibitors have revolutionized the treatment of renal cell carcinoma (RCC), but many patients do not respond to therapy and the majority develop resistant disease over time. Thus, there is increasing need for alternative immunomodulating agents. The co-inhibitory molecule T-cell immunoglobulin and ITIM domain (TIGIT) may play a role in resistance to approved immune checkpoint inhibitors and is being investigated as a potential therapeutic target. The purpose of this study was to quantify TIGIT positivity in tumor-infiltrating T cells in RCC.</p><p><strong>Methods: </strong>We employed tissue microarrays containing specimens from primary RCC tumors, adjacent normal renal tissue, and RCC metastases to quantify TIGIT within tumor-infiltrating CD3<sup>+</sup> T cells using quantitative immunofluorescent analysis. We also compared these results to TIGIT<sup>+</sup> CD3<sup>+</sup> levels in four other tumor types (melanoma, non-small cell lung, cervical, and head and neck cancers).</p><p><strong>Results: </strong>We did not observe significant differences in TIGIT positivity between primary RCC tumors and patient-matched metastatic samples. We found that the degree of TIGIT positivity in RCC is comparable to that in lung cancer but lower than that in melanoma, cervical, and head and neck cancers. Correlation analysis comparing TIGIT positivity to previously published, patient-matched spatial proteomic data by our group revealed a negative association between TIGIT and the checkpoint proteins PD-1 and LAG3.</p><p><strong>Conclusion: </strong>Our findings support careful evaluation of TIGIT expression on T cells in primary or metastatic RCC specimens for patients who may be treated with TIGIT-targeting antibodies, as increased TIGIT positivity might be associated with a greater likelihood of response to therapy.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 10","pages":"192"},"PeriodicalIF":4.6,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Predicting recurrent glioblastoma clinical outcome to immune checkpoint inhibition and low-dose bevacizumab with tumor in situ fluid circulating tumor DNA analysis.","authors":"Guangzhong Guo, Ziyue Zhang, Jiubing Zhang, Dayang Wang, Sensen Xu, Guanzheng Liu, Yushuai Gao, Jie Mei, Zhaoyue Yan, Ruijiao Zhao, Meiyun Wang, Tianxiao Li, Xingyao Bu","doi":"10.1007/s00262-024-03774-7","DOIUrl":"10.1007/s00262-024-03774-7","url":null,"abstract":"<p><strong>Objective: </strong>Most recurrent glioblastoma (rGBM) patients do not benefit from immune checkpoint inhibition, emphasizing the necessity for response biomarkers. This study evaluates whether tumor in situ fluid (TISF) circulating tumor DNA (ctDNA) could serve as a biomarker for response to low-dose bevacizumab (Bev) plus anti-PD-1 therapy in rGBM patients, aiming to enhance systemic responses to immunotherapy.</p><p><strong>Methods: </strong>In this phase II trial, 32 GBM patients with first recurrence after standard therapy were enrolled and then received tislelizumab plus low-dose Bev each cycle. TISF samples were analyzed for ctDNA using a 551-gene panel before each treatment.</p><p><strong>Results: </strong>The median progression-free survival (mPFS) and overall survival (mOS) were 8.2 months (95% CI, 5.2-11.1) and 14.3 months (95% CI, 6.5-22.1), respectively. The 12-month OS was 43.8%, and the objective response rate was 56.3%. Patients with more than 20% reduction in the mutant allele fraction and tumor mutational burden after treatment were significantly associated with better prognosis compared to baseline TISF-ctDNA. Among detectable gene mutations, patients with MUC16 mutation, EGFR mutation & amplification, SRSF2 amplification, and H3F3B amplification were significantly associated with worse prognosis.</p><p><strong>Conclusions: </strong>Low-dose Bev plus anti-PD-1 therapy significantly improves OS in rGBM patients, offering guiding significance for future individualized treatment strategies. TISF-ctDNA can monitor rGBM patients' response to combination therapy and guide treatment.</p><p><strong>Clinical trial registration: </strong>This trial is registered with ClinicalTrials.gov, NCT05540275.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 10","pages":"193"},"PeriodicalIF":4.6,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nam-Hoon Kim, Jihyun Lee, Seung-Hyun Kim, Seong-Ho Kang, Sowon Bae, Chan-Hee Yu, Jeongmin Seo, Hun-Taek Kim
{"title":"ALK5/VEGFR2 dual inhibitor TU2218 alone or in combination with immune checkpoint inhibitors enhances immune-mediated antitumor effects.","authors":"Nam-Hoon Kim, Jihyun Lee, Seung-Hyun Kim, Seong-Ho Kang, Sowon Bae, Chan-Hee Yu, Jeongmin Seo, Hun-Taek Kim","doi":"10.1007/s00262-024-03777-4","DOIUrl":"10.1007/s00262-024-03777-4","url":null,"abstract":"<p><p>Transforming growth factor β (TGFβ) is present in blood of patients who do not respond to anti-programmed cell death (ligand) 1 [PD-(L)1] treatment, and through synergy with vascular endothelial growth factor (VEGF), it helps to create an environment that promotes tumor immune evasion and immune tolerance. Therefore, simultaneous inhibition of TGFβ/VEGF is more effective than targeting TGFβ alone. In this study, the dual inhibitory mechanism of TU2218 was identified through in vitro analysis mimicking the tumor microenvironment, and its antitumor effects were analyzed using mouse syngeneic tumor models. TU2218 directly restored the activity of damaged cytotoxic T lymphocytes (CTLs) and natural killer cells inhibited by TGFβ and suppressed the activity and viability of regulatory T cells. The inactivation of endothelial cells induced by VEGF stimulation was completely ameliorated by TU2218, an effect not observed with vactosertib, which inhibits only TGFβ signaling. The combination of TU2218 and anti-PD1 therapy had a significantly greater antitumor effect than either drug alone in the poorly immunogenic B16F10 syngeneic tumor model. The mechanism of tumor reduction was confirmed by flow cytometry, which showed upregulated VCAM-1 expression in vascular cells and increased influx of CD8 + CTLs into the tumor. As another strategy, combination of anti-CTLA4 therapy and TU2218 resulted in high complete regression (CR) rates in CT26 and WEHI-164 tumor models. In particular, immunological memory generated by the combination of anti-CTLA4 and TU2218 in the CT26 model prevented the development of tumors after additional tumor cell transplantation, suggesting that the TU2218-based combination has therapeutic potential in immunotherapy.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 10","pages":"190"},"PeriodicalIF":4.6,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S C Saunderson, J C Halpin, G M Y Tan, P Shrivastava, A D McLellan
{"title":"Conversion of anti-tissue factor antibody sequences to chimeric antigen receptor and bi-specific T-cell engager format.","authors":"S C Saunderson, J C Halpin, G M Y Tan, P Shrivastava, A D McLellan","doi":"10.1007/s00262-024-03778-3","DOIUrl":"10.1007/s00262-024-03778-3","url":null,"abstract":"<p><strong>Background: </strong>The efficacy of antibody-targeted therapy of solid cancers is limited by the lack of consistent tumour-associated antigen expression. However, tumour-associated antigens shared with non-malignant cells may still be targeted using conditionally activated-antibodies, or by chimeric antigen receptor (CAR) T cells or CAR NK cells activated either by the tumour microenvironment or following 'unlocking' via multiple antigen-recognition. In this study, we have focused on tissue factor (TF; CD142), a type I membrane protein present on a range of solid tumours as a basis for future development of conditionally-activated BiTE or CAR T cells. TF is frequently upregulated on multiple solid tumours providing a selective advantage for growth, immune evasion and metastasis, as well as contributing to the pathology of thrombosis via the extrinsic coagulation pathway.</p><p><strong>Methods: </strong>Two well-characterised anti-TF monoclonal antibodies (mAb) were cloned into expression or transposon vectors to produce single chain (scFv) BiTE for assessment as CAR and CD28-CD3-based CAR or CD3-based BiTE. The affinities of both scFv formats for TF were determined by surface plasmon resonance. Jurkat cell line-based assays were used to confirm the activity of the BiTE or CAR constructs.</p><p><strong>Results: </strong>The anti-TF mAb hATR-5 and TF8-5G9 mAb were shown to maintain their nanomolar affinities following conversion into a single chain (scFv) format and could be utilised as CD28-CD3-based CAR or CD3-based BiTE format.</p><p><strong>Conclusion: </strong>Because of the broad expression of TF on a range of solid cancers, anti-TF antibody formats provide a useful addition for the development of conditionally activated biologics for antibody and cellular-based therapy.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 10","pages":"195"},"PeriodicalIF":4.6,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jianyun Jiang, Bin Wu, Ying Sun, Jun Xiang, Chunying Shen, Xiayun He, Hongmei Ying, Zuguang Xia
{"title":"Anlotinib reversed resistance to PD-1 inhibitors in recurrent and metastatic head and neck cancers: a real-world retrospective study.","authors":"Jianyun Jiang, Bin Wu, Ying Sun, Jun Xiang, Chunying Shen, Xiayun He, Hongmei Ying, Zuguang Xia","doi":"10.1007/s00262-024-03784-5","DOIUrl":"10.1007/s00262-024-03784-5","url":null,"abstract":"<p><p>Patients with recurrent or metastatic head and neck cancers (R/M HNCs) are prone to developing resistance after immunotherapy. This retrospective real-world study aims to investigate whether the addition of anlotinib can reverse resistance to PD-1 inhibitors (PD-1i) and evaluate the efficacy and safety of this combination in R/M HNCs. Main outcomes included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), and safety. Potential biomarkers included PD-L1 expression, lipid index, and genomic profiling. Twenty-one patients with R/M HNCs were included, including 11 nasopharyngeal carcinoma (NPC), five head and neck squamous cell carcinoma (HNSCC), three salivary gland cancers (SGC), and two nasal cavity or paranasal sinus cancers (NC/PNC). Among all patients, ORR was 47.6% (95% CI: 28.6-66.7), with 2 (9.5%) complete response; DCR was 100%. At the median follow-up of 17.1 months, the median PFS and OS were 14.3 months (95% CI: 5.9-NR) and 16.7 months (95% CI:8.4-NR), respectively. The median DOR was 11.2 months (95% CI: 10.1-NR). As per different diseases, the ORR was 45.5% for NPC, 60.0% for HNSCC, 66.7% for SGC, and 50.0% for NC/PNC. Most treatment-related adverse events (TRAEs) were grade 1 or 2 (88.9%). The most common grades 3-4 TRAE was hypertension (28.6%), and two treatment-related deaths occurred due to bleeding. Therefore, adding anlotinib to the original PD-1i could reverse PD-1 blockade resistance, with a favorable response rate, prolonged survival, and acceptable toxicity, indicating the potential as a second-line and subsequent therapy choice in R/M HNCs.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 10","pages":"199"},"PeriodicalIF":4.6,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eswara Rao Puppala, Long Wu, Xiaoxuan Fan, Xuefang Cao
{"title":"CD27 signaling inhibits tumor growth and metastasis via CD8 + T cell-independent mechanisms in the B16-F10 melanoma model.","authors":"Eswara Rao Puppala, Long Wu, Xiaoxuan Fan, Xuefang Cao","doi":"10.1007/s00262-024-03780-9","DOIUrl":"10.1007/s00262-024-03780-9","url":null,"abstract":"<p><p>CD27 belongs to the tumor necrosis factor receptor superfamily and acts as a co-stimulatory molecule, modulating T and B cell responses. CD27 stimulation enhances T cell survival and effector functions, thus providing opportunities to develop therapeutic strategies. The current study aims to investigate the role of endogenous CD27 signaling in tumor growth and metastasis. CD8 + T cell-specific CD27 knockout (CD8Cre-CD27fl) mice were developed, while global CD27 knockout (KO) mice were also used in our studies. Flow cytometry analyses confirmed that CD27 was deleted specifically from CD8 + T cells without affecting CD4 + T cells, B cells, and HSPCs in the CD8Cre-CD27fl mice, while CD27 was deleted from all cell types in global CD27 KO mice. Tumor growth and metastasis studies were performed by injecting B16-F10 melanoma cells subcutaneously (right flank) or intravenously into the mice. We have found that global CD27 KO mice succumbed to significantly accelerated tumor growth compared to WT controls. In addition, global CD27 KO mice showed a significantly higher burden of metastatic tumor nests in the lungs compared to WT controls. However, there was no significant difference in tumor growth curves, survival, metastatic tumor nest counts between the CD8Cre-CD27fl mice and WT controls. These results suggest that endogenous CD27 signaling inhibits tumor growth and metastasis via CD8 + T cell-independent mechanisms in this commonly used melanoma model, presumably through stimulating antitumor activities of other types of immune cells.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"73 10","pages":"198"},"PeriodicalIF":4.6,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}