17 results on '"Allison, James P."'
Search Results
2. Immune checkpoint therapy: Forging ahead.
- Author
-
Sharma, Padmanee and Allison, James P.
- Subjects
IMMUNE checkpoint proteins ,DNA mismatch repair ,T cell receptors ,IMMUNOREGULATION ,REGULATORY T cells ,ANTIGEN presenting cells ,COMPUTATIONAL biology - Published
- 2022
- Full Text
- View/download PDF
3. ARID1A mutation plus CXCL13 expression act as combinatorial biomarkers to predict responses to immune checkpoint therapy in mUCC.
- Author
-
Goswami, Sangeeta, Chen, Yulong, Anandhan, Swetha, Szabo, Peter M., Basu, Sreyashi, Blando, Jorge M., Liu, Wenbin, Zhang, Jan, Natarajan, Seanu Meena, Xiong, Liangwen, Guan, Baoxiang, Yadav, Shalini Singh, Saci, Abdel, Allison, James P., Galsky, Matthew D., and Sharma, Padmanee
- Subjects
TRANSITIONAL cell carcinoma ,IMMUNE response ,TUMOR markers ,BLADDER cancer ,BIOMARKERS ,BIOLOGICAL tags ,PHARMACOGENOMICS ,PROGRAMMED cell death 1 receptors - Abstract
Two markers can be better than one: Therapies targeting immune checkpoints in cancer are achieving increasing prominence because they can achieve long-lasting responses in patients with difficult-to-treat tumors. Unfortunately, not all tumors respond to these treatments, and it is not clear how to identify patients most likely to benefit. Previous studies have suggested individual biomarkers, such as expression of the immune checkpoints themselves, but this was not sufficient. To address this problem, Goswami et al. investigated potential biomarker combinations and identified a genetic change and an immune marker, which together helped predict response to immune checkpoint therapy in multiple cohorts of patients with metastatic urothelial carcinoma. Immune checkpoint therapy (ICT) can produce durable antitumor responses in metastatic urothelial carcinoma (mUCC); however, the responses are not universal. Despite multiple approvals of ICT in mUCC, we lack predictive biomarkers to guide patient selection. The identification of biomarkers may require interrogation of both the tumor mutational status and the immune microenvironment. Through multi-platform immuno-genomic analyses of baseline tumor tissues, we identified the mutation of AT-rich interactive domain-containing protein 1A (ARID1A) in tumor cells and expression of immune cytokine CXCL13 in the baseline tumor tissues as two predictors of clinical responses in a discovery cohort (n = 31). Further, reverse translational studies revealed that CXCL13
−/− tumor-bearing mice were resistant to ICT, whereas ARID1A knockdown enhanced sensitivity to ICT in a murine model of bladder cancer. Next, we tested the clinical relevance of ARID1A mutation and baseline CXCL13 expression in two independent confirmatory cohorts (CheckMate275 and IMvigor210). We found that ARID1A mutation and expression of CXCL13 in the baseline tumor tissues correlated with improved overall survival (OS) in both confirmatory cohorts (CheckMate275, CXCL13 data, n = 217; ARID1A data, n = 139, and IMvigor210, CXCL13 data, n = 348; ARID1A data, n = 275). We then interrogated CXCL13 expression plus ARID1A mutation as a combination biomarker in predicting response to ICT in CheckMate275 and IMvigor210. Combination of the two biomarkers in baseline tumor tissues suggested improved OS compared to either single biomarker. Cumulatively, this study revealed that the combination of CXCL13 plus ARID1A may improve prediction capability for patients receiving ICT. [ABSTRACT FROM AUTHOR]- Published
- 2020
- Full Text
- View/download PDF
4. Neoantigen responses, immune correlates, and favorable outcomes after ipilimumab treatment of patients with prostate cancer.
- Author
-
Subudhi, Sumit K., Vence, Luis, Zhao, Hao, Blando, Jorge, Yadav, Shalini S., Xiong, Qing, Reuben, Alexandre, Aparicio, Ana, Corn, Paul G., Chapin, Brian F., Pisters, Louis L., Troncoso, Patricia, Tidwell, Rebecca Slack, Thall, Peter, Wu, Chang-Jiun, Zhang, Jianhua, Logothetis, Christopher L., Futreal, Andrew, Allison, James P., and Sharma, Padmanee
- Subjects
PROSTATE cancer patients ,CASTRATION-resistant prostate cancer ,ANDROGEN drugs ,INTRA-aortic balloon counterpulsation ,PROGNOSIS - Abstract
New ideas about neoantigens: Tumors with a low mutational burden are thought to have fewer neoantigens available for T cells to respond to and thus are not necessarily considered for checkpoint blockade therapy. Subudhi et al. treated patients with metastatic castration-resistant prostate cancer, which has a relatively low mutation burden, with ipilimumab. Patients who responded to the treatment had a T cell response signature and detectable neoantigen immunity. These results indicate that checkpoint blockade therapy with ipilimumab can instigate T cell responses to tumor neoantigens despite the tumor mutational burden status. Tumors with high mutational burden (TMB) tend to be responsive to immune checkpoint blockade (ICB) because there are neoantigens available for targeting by reinvigorated T cells, whereas those with low TMB demonstrate limited clinical responses. To determine whether antigen-specific T cell responses can be elicited after treatment with ICB in cancers that have a low TMB, we conducted a clinical trial with ipilimumab in 30 patients with metastatic castration-resistant prostate cancer. We identified two distinct cohorts by survival and progression times: "favorable" (n = 9) and "unfavorable" (n = 10). Patients in the favorable cohort had high intratumoral CD8 T cell density and IFN-γ response gene signature and/or antigen-specific T cell responses. Two patients with a relatively low TMB had T cell responses against unique neoantigens. Moreover, six of nine patients in the favorable group are still alive at the time of analysis, with survival ranging from 33 to 54 months after treatment. All 10 patients in the unfavorable cohort have succumbed to their disease and had survival ranging from 0.6 to 10.3 months. Collectively, our data indicate that immunological correlates associated with effector T cell responses are observed in patients with metastatic prostate cancer who benefit from ICB. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
5. Enhancement of antitumor immunity by CTLA-4 blockade
- Author
-
Leach, Dana R., Krummel, Matthew F., and Allison, James P.
- Subjects
Antineoplastic agents -- Research ,Immunity -- Research ,Circadian rhythms -- Research ,Antimitotic agents -- Research ,Science and technology ,Research - Abstract
One reason for the poor immunogenicity of many tumors may be that they cannot provide signals for CD28-mediated costimulation necessary to fully activate T cells. it has recently become apparent that CTLA-4, a second counterreceptor for the B7 family of costimulatory molecules, is a negative regulator of T cell activation. Here, in vivo administration of antibodies t6 CTLA-4 resulted in the rejection of tumors, including preestablished tumors. Furthermore, this rejection resulted in immunity to a secondary exposure to tumor cells. These results suggest that, blockade of the inhibitory effects of CTLA-4 can allow for, and potentiate, effective immune responses against tumor cells., Despite expressing antigens recognizable by a host's immune system, tumors are very poor in initiating effective immune responses. One reason for this poor immunogenicity may be that the presentation of [...]
- Published
- 1996
6. Tumor rejection after direct costimulation of CD8+ T Cells by B7-transfected melanoma cells
- Author
-
Townsend, Sarah E. and Allison, James P.
- Subjects
CD8 lymphocytes -- Physiological aspects -- Research ,T cells -- Research -- Physiological aspects ,Immunological adjuvants -- Research ,Melanoma -- Physiological aspects -- Research ,Science and technology ,Physiological aspects ,Research - Abstract
A variety of tumors are potentially immunogenic but do not stimulate an effective anti-tumor immune response in vivo. Tumors may be capable of delivering antigen-specific signals to T cells, but [...]
- Published
- 1993
7. Recognition of self antigens by skin-derived T cells with invariant gamma-delta antigen receptors
- Author
-
Havran, Wendy L., Chien, Yueh-Hsiu, and Allison, James P.
- Subjects
T cells -- Receptors ,Antigen receptors, T cell -- Research ,Immune recognition -- Research ,Science and technology ,Research - Abstract
IN MICE, MOST T CELLS IN THE LYMphoid tissues express diverse antigen receptors that consist of α and β chains and recognize antigens bound to self major histocompatibility complex (MHC) [...]
- Published
- 1991
8. The yin and yang of T cell costimulation
- Author
-
Allison, James P. and Krummel, Matthew F.
- Subjects
T cells -- Research ,Antigen presenting cells -- Research ,Immune response -- Regulation ,Science and technology ,Research - Abstract
T cells require two types of signals from antigen-presenting cells (APCs) for activation and subsequent differentiation to effector function. One is an antigen-specific signal provided by interactions between the T [...]
- Published
- 1995
9. The future of immune checkpoint therapy.
- Author
-
Sharma, Padmanee and Allison, James P.
- Subjects
- *
CANCER immunotherapy , *T cells , *TARGETED drug delivery , *TUMOR immunology , *IMMUNE response , *CYTOTOXIC T lymphocyte-associated molecule-4 , *MAJOR histocompatibility complex , *ANTIGENS - Abstract
Immune checkpoint therapy, which targets regulatory pathways in T cells to enhance antitumor immune responses, has led to important clinical advances and provided a new weapon against cancer. This therapy has elicited durable clinical responses and, in a fraction of patients, long-term remissions where patients exhibit no clinical signs of cancer for many years. The way forward for this class of novel agents lies in our ability to understand human immune responses in the tumor microenvironment. This will provide valuable information regarding the dynamic nature of the immune response and regulation of additional pathways that will need to be targeted through combination therapies to provide survival benefit for greater numbers of patients. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
10. Localized Oncolytic Virotherapy Overcomes Systemic Tumor Resistance to Immune Checkpoint Blockade Immunotherapy.
- Author
-
Zamarin, Dmitriy, Holmgaard, Rikke B., Subudhi, Sumit K., Joon Seok Park, Mansour, Mena, Palese, Peter, Merghoub, Taha, Wolchok, Jedd D., and Allison, James P.
- Published
- 2014
- Full Text
- View/download PDF
11. Lloyd J. Old (1933-2011).
- Author
-
Sharma, Padmanee and Allison, James P.
- Subjects
- *
IMMUNOLOGISTS - Abstract
An obituary is presented for immunologist Lloyd J. Old.
- Published
- 2012
- Full Text
- View/download PDF
12. Aire-Dependent Thymic Development of Tumor-Associated Regulatory T Cells.
- Author
-
Malchow, Sven, Leventhal, Daniel S., Nishi, Saki, Fischer, Benjamin I., Shen, Lynn, Paner, Gladell P., Amit, Ayelet S., Kang, Chulho, Geddes, Jenna E., Allison, James P., Socci, Nicholas D., and Savage, Peter A.
- Subjects
- *
IMMUNOLOGY , *T cells , *AUTOIMMUNITY -- Molecular aspects , *ANTIGENS , *T cell differentiation , *SUPPRESSOR cells , *CANCER invasiveness , *MOLECULAR immune response , *IMMUNOREGULATION - Abstract
Despite considerable interest in the modulation of tumor-associated Foxp3+ regulatory T cells (Tregs) for therapeutic benefit, little is known about the developmental origins of these cells and the nature of the antigens that they recognize. We identified an endogenous population of antigen-specific Tregs (termed MJ23 Tregs) found recurrently enriched in the tumors of mice with oncogene-driven prostate cancer. MJ23 Tregs were not reactive to a tumor-specific antigen but instead recognized a prostate-associated antigen that was present in tumor-free mice. MJ23 Tregs underwent autoimmune regulator (Aire)-dependent thymic development in both mate and female mice. Thus, Aire-mediated expression of peripheral tissue antigens drives the thymic development of a subset of organ-specific Tregs, which are likely coopted by tumors developing within the associated organ. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
13. Recognition of a Ubiquitous Self Antigen by Prostate Cancer — Infiltrating CD8+ T Lymphocytes.
- Author
-
Savage, Peter A., Vosseller, Keith, Chutho Kang, Larimore, Kevin, Riedet, Elyn, Wojnoonski, Kathleen, Jungbluth, Achim A., and Allison, James P.
- Subjects
- *
PROSTATE cancer , *TUMORS , *INCURABLE diseases , *T cells , *ANTIGENS , *IMMUNOTHERAPY , *ADENOCARCINOMA , *MICE , *CANCER research - Abstract
Substantial evidence exists that many tumors can be specifically recognized by CD8+ T lymphocytes. The definition of antigens targeted by these cells is paramount for the development of effective immunotherapeutic strategies for treating human cancers. In a screen for endogenous tumor-associated T cell responses in a primary mouse model of prostatic adenocarcinoma, we identified a naturally arising CD8+ T cell response that is reactive to a peptide derived from histone H4. Despite the ubiquitous nature of histones, T cell recognition of histone H4 peptide was specifically associated with the presence of prostate cancer in these mice. Thus, the repertoire of antigens recognized by tumor-infiltrating T cells is broader than previously thought and includes peptides derived from ubiquitous self antigens that are normally sequestered from immune detection. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
14. A phase 1-2 trial of sitravatinib and nivolumab in clear cell renal cell carcinoma following progression on antiangiogenic therapy.
- Author
-
Msaouel P, Goswami S, Thall PF, Wang X, Yuan Y, Jonasch E, Gao J, Campbell MT, Shah AY, Corn PG, Tam AL, Ahrar K, Rao P, Sircar K, Cohen L, Basu S, Duan F, Jindal S, Zhang Y, Chen H, Yadav SS, Shazer R, Der-Torossian H, Allison JP, Sharma P, and Tannir NM
- Subjects
- Angiogenesis Inhibitors therapeutic use, Anilides, Female, Humans, Male, Nivolumab therapeutic use, Pyridines, Tumor Microenvironment, Carcinoma, Renal Cell drug therapy, Carcinoma, Renal Cell pathology, Kidney Neoplasms drug therapy, Kidney Neoplasms pathology, Liver Neoplasms drug therapy
- Abstract
The accumulation of immune-suppressive myeloid cells is a critical determinant of resistance to anti-programmed death-1 (PD-1) therapy in advanced clear cell renal cell carcinoma (ccRCC). In preclinical models, the tyrosine kinase inhibitor sitravatinib enhanced responses to anti-PD-1 therapy by modulating immune-suppressive myeloid cells. We conducted a phase 1-2 trial to choose an optimal sitravatinib dose combined with a fixed dose of nivolumab in 42 immunotherapy-naïve patients with ccRCC refractory to prior antiangiogenic therapies. The combination demonstrated no unexpected toxicities and achieved an objective response rate of 35.7% and a median progression-free survival of 11.7 months, with 80.1% of patients alive after a median follow-up of 18.7 months. Baseline peripheral blood neutrophil-to-lymphocyte ratio correlated with response to sitravatinib and nivolumab. Patients with liver metastases showed durable responses comparable to patients without liver metastases. In addition, correlative studies demonstrated reduction of immune-suppressive myeloid cells in the periphery and tumor microenvironment following sitravatinib treatment. This study provides a rationally designed combinatorial strategy to improve outcomes of anti-PD-1 therapy in advanced ccRCC.
- Published
- 2022
- Full Text
- View/download PDF
15. Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response.
- Author
-
Spencer CN, McQuade JL, Gopalakrishnan V, McCulloch JA, Vetizou M, Cogdill AP, Khan MAW, Zhang X, White MG, Peterson CB, Wong MC, Morad G, Rodgers T, Badger JH, Helmink BA, Andrews MC, Rodrigues RR, Morgun A, Kim YS, Roszik J, Hoffman KL, Zheng J, Zhou Y, Medik YB, Kahn LM, Johnson S, Hudgens CW, Wani K, Gaudreau PO, Harris AL, Jamal MA, Baruch EN, Perez-Guijarro E, Day CP, Merlino G, Pazdrak B, Lochmann BS, Szczepaniak-Sloane RA, Arora R, Anderson J, Zobniw CM, Posada E, Sirmans E, Simon J, Haydu LE, Burton EM, Wang L, Dang M, Clise-Dwyer K, Schneider S, Chapman T, Anang NAS, Duncan S, Toker J, Malke JC, Glitza IC, Amaria RN, Tawbi HA, Diab A, Wong MK, Patel SP, Woodman SE, Davies MA, Ross MI, Gershenwald JE, Lee JE, Hwu P, Jensen V, Samuels Y, Straussman R, Ajami NJ, Nelson KC, Nezi L, Petrosino JF, Futreal PA, Lazar AJ, Hu J, Jenq RR, Tetzlaff MT, Yan Y, Garrett WS, Huttenhower C, Sharma P, Watowich SS, Allison JP, Cohen L, Trinchieri G, Daniel CR, and Wargo JA
- Subjects
- Animals, Cohort Studies, Fatty Acids, Volatile analysis, Fecal Microbiota Transplantation, Feces chemistry, Feces microbiology, Female, Humans, Immunotherapy, Male, Melanoma immunology, Melanoma microbiology, Melanoma, Experimental immunology, Melanoma, Experimental microbiology, Melanoma, Experimental therapy, Mice, Mice, Inbred C57BL, Progression-Free Survival, T-Lymphocytes, Dietary Fiber, Gastrointestinal Microbiome, Immune Checkpoint Inhibitors therapeutic use, Melanoma therapy, Probiotics
- Abstract
Gut bacteria modulate the response to immune checkpoint blockade (ICB) treatment in cancer, but the effect of diet and supplements on this interaction is not well studied. We assessed fecal microbiota profiles, dietary habits, and commercially available probiotic supplement use in melanoma patients and performed parallel preclinical studies. Higher dietary fiber was associated with significantly improved progression-free survival in 128 patients on ICB, with the most pronounced benefit observed in patients with sufficient dietary fiber intake and no probiotic use. Findings were recapitulated in preclinical models, which demonstrated impaired treatment response to anti–programmed cell death 1 (anti–PD-1)–based therapy in mice receiving a low-fiber diet or probiotics, with a lower frequency of interferon-γ–positive cytotoxic T cells in the tumor microenvironment. Together, these data have clinical implications for patients receiving ICB for cancer.
- Published
- 2021
- Full Text
- View/download PDF
16. Integrated molecular analysis of tumor biopsies on sequential CTLA-4 and PD-1 blockade reveals markers of response and resistance.
- Author
-
Roh W, Chen PL, Reuben A, Spencer CN, Prieto PA, Miller JP, Gopalakrishnan V, Wang F, Cooper ZA, Reddy SM, Gumbs C, Little L, Chang Q, Chen WS, Wani K, De Macedo MP, Chen E, Austin-Breneman JL, Jiang H, Roszik J, Tetzlaff MT, Davies MA, Gershenwald JE, Tawbi H, Lazar AJ, Hwu P, Hwu WJ, Diab A, Glitza IC, Patel SP, Woodman SE, Amaria RN, Prieto VG, Hu J, Sharma P, Allison JP, Chin L, Zhang J, Wargo JA, and Futreal PA
- Subjects
- Biomarkers, Tumor metabolism, Biopsy, CTLA-4 Antigen metabolism, Clone Cells, Cohort Studies, DNA Copy Number Variations genetics, Gene Dosage, Genome, Humans, Mutation genetics, Neoplasms genetics, Neoplasms immunology, Programmed Cell Death 1 Receptor metabolism, T-Lymphocytes immunology, CTLA-4 Antigen antagonists & inhibitors, Drug Resistance, Neoplasm, Neoplasms drug therapy, Neoplasms pathology, Programmed Cell Death 1 Receptor antagonists & inhibitors
- Abstract
Immune checkpoint blockade produces clinical benefit in many patients. However, better biomarkers of response are still needed, and mechanisms of resistance remain incompletely understood. To address this, we recently studied a cohort of melanoma patients treated with sequential checkpoint blockade against cytotoxic T lymphocyte antigen-4 (CTLA-4) followed by programmed death receptor-1 (PD-1) and identified immune markers of response and resistance. Building on these studies, we performed deep molecular profiling including T cell receptor sequencing and whole-exome sequencing within the same cohort and demonstrated that a more clonal T cell repertoire was predictive of response to PD-1 but not CTLA-4 blockade. Analysis of CNAs identified a higher burden of copy number loss in nonresponders to CTLA-4 and PD-1 blockade and found that it was associated with decreased expression of genes in immune-related pathways. The effect of mutational load and burden of copy number loss on response was nonredundant, suggesting the potential utility of a combinatorial biomarker to optimize patient care with checkpoint blockade therapy., (Copyright © 2017, American Association for the Advancement of Science.)
- Published
- 2017
- Full Text
- View/download PDF
17. Retrospective. Lloyd J. Old (1933-2011).
- Author
-
Sharma P and Allison JP
- Subjects
- Animals, Cancer Vaccines history, Cancer Vaccines therapeutic use, History, 20th Century, History, 21st Century, Humans, Mice, Neoplasms history, Neoplasms therapy, United States, Neoplasms immunology
- Published
- 2012
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.