Rakesh Jain
Harvard University
H-index: 217
North America-United States
Description
Rakesh Jain, With an exceptional h-index of 217 and a recent h-index of 120 (since 2020), a distinguished researcher at Harvard University,
His recent articles reflect a diverse array of research interests and contributions to the field:
Reprogramming the Intrahepatic Cholangiocarcinoma Immune Microenvironment by Chemotherapy and CTLA-4 Blockade Enhances Anti–PD-1 Therapy
Inhibition of CXCR4 enhances the efficacy of radiotherapy in metastatic prostate cancer models
Anti-VEGF therapy improves EGFR-vIII-CAR-T cell delivery and efficacy in syngeneic glioblastoma models in mice
Desmoplasia in cervical cancer is associated with a more aggressive tumor phenotype
Mechanistic model for booster doses effectiveness in healthy, cancer, and immunosuppressed patients infected with SARS-CoV-2
Multicenter, prospective, phase II study of maintenance bevacizumab for children and adults with NF2-related schwannomatosis and progressive vestibular …
Antigen presentation deficiency, mesenchymal differentiation, and resistance to immunotherapy in the murine syngeneic CT2A tumor model
Computational simulations of tumor growth and treatment response: Benefits of high-frequency, low-dose drug regimens and concurrent vascular normalization
Professor Information
University | Harvard University |
---|---|
Position | Massachusetts General Hospital, Harvard Medical School, Carnegie Mellon, Columbia, Delaware |
Citations(all) | 209662 |
Citations(since 2020) | 61357 |
Cited By | 173630 |
hIndex(all) | 217 |
hIndex(since 2020) | 120 |
i10Index(all) | 532 |
i10Index(since 2020) | 408 |
University Profile Page | Harvard University |
Top articles of Rakesh Jain
Reprogramming the Intrahepatic Cholangiocarcinoma Immune Microenvironment by Chemotherapy and CTLA-4 Blockade Enhances Anti–PD-1 Therapy
Intrahepatic cholangiocarcinoma (ICC) has limited therapeutic options and a dismal prognosis. Adding blockade of the anti–programmed cell death protein (PD)-1 pathway to gemcitabine/cisplatin chemotherapy has recently shown efficacy in biliary tract cancers but with low response rates. Here, we studied the effects of anti–cytotoxic T lymphocyte antigen (CTLA)-4 when combined with anti–PD-1 and gemcitabine/cisplatin in orthotopic murine models of ICC. This combination therapy led to substantial survival benefits and reduction of morbidity in two aggressive ICC models that were resistant to immunotherapy alone. Gemcitabine/cisplatin treatment increased tumor-infiltrating lymphocytes and normalized the ICC vessels and, when combined with dual CTLA-4/PD-1 blockade, increased the number of activated CD8+Cxcr3+IFNγ+ T cells. CD8+ T cells were necessary for the therapeutic benefit because the …
Authors
Jiang Chen,Zohreh Amoozgar,Xin Liu,Shuichi Aoki,Zelong Liu,Sarah M Shin,Aya Matsui,Alexei Hernandez,Zhangya Pu,Stefan Halvorsen,Pin-Ji Lei,Meenal Datta,Lingling Zhu,Zhiping Ruan,Lei Shi,Daniel Staiculescu,Koetsu Inoue,Lance L Munn,Dai Fukumura,Peigen Huang,Slim Sassi,Nabeel Bardeesy,Won Jin Ho,Rakesh K Jain,Dan G Duda
Journal
Cancer Immunology Research
Published Date
2024/2/20
Inhibition of CXCR4 enhances the efficacy of radiotherapy in metastatic prostate cancer models
Simple Summary We examined the expression of SDF1α and its cognate receptor CXCR4 in human prostate cancer (PCa) lesions and the impact of CXCR4 inhibition alone and in combination with single-dose irradiation in orthotopic PCa models in mice. Both SDF1α and CXCR4 were highly expressed in primary and bone metastatic human PCa samples. Inhibiting CXCR4 activity in PCa cells abrogated SDF1α-induced invasion but did not sensitize them to irradiation in vitro. In orthotopic primary and bone metastatic PCa models, treatment with the CXCR4 antagonist AMD3100 alone was ineffective, but when added to radiotherapy, it significantly inhibited metastatic tumor growth. The mechanisms of AMD3100 included normalization of bone metastatic PCa vasculature. These results support testing SDF1α/CXCR4 inhibitors with radiotherapy in metastatic PCa patients. Abstract Radiotherapy (RT) is a standard treatment for patients with advanced prostate cancer (PCa). Previous preclinical studies showed that SDF1α/CXCR4 axis could mediate PCa metastasis (most often to the bones) and cancer resistance to RT. We found high levels of expression for both SDF1α and its receptor CXCR4 in primary and metastatic PCa tissue samples. In vitro analyses using PCa cells revealed an important role of CXCR4 in cell invasion but not radiotolerance. Pharmacologic inhibition of CXCR4 using AMD3100 showed no efficacy in orthotopic primary and bone metastatic PCa models. However, when combined with RT, AMD3100 potentiated the effect of local single-dose RT (12 Gy) in both models. Moreover, CXCR4 …
Authors
Nisha Gupta,Hiroki Ochiai,Yoshinori Hoshino,Sebastian Klein,Jozef Zustin,Rakesh R Ramjiawan,Shuji Kitahara,Nir Maimon,Despina Bazou,Sarah Chiang,Sen Li,Daniel H Schanne,Rakesh K Jain,Lance L Munn,Peigen Huang,Sergey V Kozin,Dan G Duda
Journal
Cancers
Published Date
2023/2/6
Anti-VEGF therapy improves EGFR-vIII-CAR-T cell delivery and efficacy in syngeneic glioblastoma models in mice
Chimeric antigen receptor (CAR)-T cells have revolutionized the treatment of multiple types of hematological malignancies, but have shown limited efficacy in patients with glioblastoma (GBM) or other solid tumors. This may be largely due to the immunosuppressive tumor microenvironment (TME) that compromises CAR-T cells’ delivery and antitumor activity. We previously showed that blocking vascular endothelial growth factor (VEGF) signaling can normalize tumor vessels in murine and human tumors, including GBM, breast, liver, and rectal carcinomas. Moreover, we demonstrated that vascular normalization can improve the delivery of CD8+ T cells and the efficacy of immunotherapy in breast cancer models in mice. In fact, the US FDA (Food and drug administration) has approved seven different combinations of anti-VEGF drugs and immune checkpoint blockers for liver, kidney, lung and endometrial cancers in …
Authors
Xinyue Dong,Jun Ren,Zohreh Amoozgar,Somin Lee,Meenal Datta,Sylvie Roberge,Mark Duquette,Dai Fukumura,Rakesh K Jain
Journal
Journal for ImmunoTherapy of Cancer
Published Date
2023
Desmoplasia in cervical cancer is associated with a more aggressive tumor phenotype
In cancer of the uterine cervix, the role of desmoplasia, i.e., peritumoral stromal remodeling characterized by fibroblast activation and increased extracellular matrix deposition, is not established. We conducted a retrospective cohort study based on data from 438 patients who had undergone surgical treatment for cervical cancer as part of the prospective Leipzig Mesometrial Resection study between 1999 and 2021. Using non-parametric tests, Kaplan–Meier plotting, and Cox regression modeling, we calculated the prognostic impact of desmoplasia and its association with other risk factors. Desmoplasia was present in 80.6% of cases and was associated with a higher frequency of lymphovascular space involvement (76.5 vs. 56.5%, p < 0.001) and venous infiltration (14.4 vs. 2.4%, p < 0.001). Lymph node metastasis (23.0 vs. 11.8%, p < 0.05) and parametrial involvement (47.3 vs. 17.6%, p < 0.0001) were …
Authors
Benjamin Wolf,Laura Weydandt,Nadja Dornhöfer,Grit Gesine Ruth Hiller,Anne Kathrin Höhn,Ivonne Nel,Rakesh K Jain,Lars-Christian Horn,Bahriye Aktas
Journal
Scientific Reports
Published Date
2023/11/2
Mechanistic model for booster doses effectiveness in healthy, cancer, and immunosuppressed patients infected with SARS-CoV-2
SARS-CoV-2 vaccines are effective at limiting disease severity, but effectiveness is lower among patients with cancer or immunosuppression. Effectiveness wanes with time and varies by vaccine type. Moreover, previously prescribed vaccines were based on the ancestral SARS-CoV-2 spike-protein that emerging variants may evade. Here, we describe a mechanistic mathematical model for vaccination-induced immunity. We validate it with available clinical data and use it to simulate the effectiveness of vaccines against viral variants with lower antigenicity, increased virulence, or enhanced cell binding for various vaccine platforms. The analysis includes the omicron variant as well as hypothetical future variants with even greater immune evasion of vaccine-induced antibodies and addresses the potential benefits of the new bivalent vaccines. We further account for concurrent cancer or underlying …
Authors
Chrysovalantis Voutouri,C Corey Hardin,Vivek Naranbhai,Mohammad R Nikmaneshi,Melin J Khandekar,Justin F Gainor,Triantafyllos Stylianopoulos,Lance L Munn,Rakesh K Jain
Journal
Proceedings of the National Academy of Sciences
Published Date
2023/1/17
Multicenter, prospective, phase II study of maintenance bevacizumab for children and adults with NF2-related schwannomatosis and progressive vestibular …
Background Prospective data on maintenance therapy with bevacizumab for persons with NF2-related schwannomatosis (NF2-SWN) is lacking. In this prospective multicenter phase II study, we evaluated the efficacy, safety, and tolerability of bevacizumab for maintenance therapy in children and adults with NF2-SWN and hearing loss due to vestibular schwannomas (VS). Methods Following induction therapy, participants received bevacizumab 5 mg/kg every 3 weeks for 18 months. Participants were monitored for changes in hearing, tumor size, and quality of life (QOL), and for adverse events. Hearing loss was defined as a statistically significant decline in word recognition score (WRS) or pure-tone average compared to the study baseline; tumor growth was defined as >20% increase in volume compared to baseline. Results Twenty participants with NF2 …
Authors
Scott R Plotkin,Jeffrey Allen,Girish Dhall,Jian L Campian,D Wade Clapp,Michael J Fisher,Rakesh K Jain,James Tonsgard,Nicole J Ullrich,Coretta Thomas,Lloyd J Edwards,Bruce Korf,Roger Packer,Matthias A Karajannis,Jaishri O Blakeley
Journal
Neuro-oncology
Published Date
2023/8/1
Antigen presentation deficiency, mesenchymal differentiation, and resistance to immunotherapy in the murine syngeneic CT2A tumor model
Background The GL261 and CT2A syngeneic tumor lines are frequently used as immunocompetent orthotopic mouse models of human glioblastoma (huGBM) but demonstrate distinct differences in their responses to immunotherapy. Methods To decipher the cell-intrinsic mechanisms that drive immunotherapy resistance in CT2A-luc and to define the aspects of human cancer biology that these lines can best model, we systematically compared their characteristics using whole exome and transcriptome sequencing, and protein analysis through immunohistochemistry, Western blot, flow cytometry, immunopeptidomics, and phosphopeptidomics. Results The transcriptional profiles of GL261-luc2 and CT2A-luc tumors resembled those of some huGBMs, despite neither line sharing the essential genetic or histologic features of huGBM. Both models exhibited striking hypermutation, with clonal hotspot mutations in RAS genes (Kras p.G12C in GL261-luc2 and Nras p.Q61L in CT2A-luc). CT2A-luc distinctly displayed mesenchymal differentiation, upregulated angiogenesis, and multiple defects in antigen presentation machinery (e.g. Tap1 p.Y488C and Psmb8 p.A275P mutations) and interferon response pathways (e.g. copy number losses of loci including IFN genes and reduced phosphorylation of JAK/STAT pathway members). The defect in MHC class I expression could be overcome in CT2A-luc by interferon-γ treatment, which may underlie the modest efficacy of some immunotherapy combinations. Additionally, CT2A-luc demonstrated substantial baseline secretion of the CCL-2, CCL-5, and CCL-22 chemokines, which play important roles as …
Authors
J Bryan Iorgulescu,Neil Ruthen,Ryuhjin Ahn,Eleni Panagioti,Prafulla C Gokhale,Martha Neagu,Maria C Speranza,Benjamin K Eschle,Kara M Soroko,Raziye Piranlioglu,Meenal Datta,Shanmugarajan Krishnan,Kathleen B Yates,Gregory J Baker,Rakesh K Jain,Mario L Suvà,Donna Neuberg,Forest M White,E Antonio Chiocca,Gordon J Freeman,Arlene H Sharpe,Catherine J Wu,David A Reardon
Journal
Frontiers in immunology
Published Date
2023/12/28
Computational simulations of tumor growth and treatment response: Benefits of high-frequency, low-dose drug regimens and concurrent vascular normalization
Implementation of effective cancer treatment strategies requires consideration of how the spatiotemporal heterogeneities within the tumor microenvironment (TME) influence tumor progression and treatment response. Here, we developed a multi-scale three-dimensional mathematical model of the TME to simulate tumor growth and angiogenesis and then employed the model to evaluate an array of single and combination therapy approaches. Treatments included maximum tolerated dose or metronomic (i.e., frequent low doses) scheduling of anti-cancer drugs combined with anti-angiogenic therapy. The results show that metronomic therapy normalizes the tumor vasculature to improve drug delivery, modulates cancer metabolism, decreases interstitial fluid pressure and decreases cancer cell invasion. Further, we find that combining an anti-cancer drug with anti-angiogenic treatment enhances tumor killing and reduces drug accumulation in normal tissues. We also show that combined anti-angiogenic and anti-cancer drugs can decrease cancer invasiveness and normalize the cancer metabolic microenvironment leading to reduced hypoxia and hypoglycemia. Our model simulations suggest that vessel normalization combined with metronomic cytotoxic therapy has beneficial effects by enhancing tumor killing and limiting normal tissue toxicity.
Authors
Mohammad R Nikmaneshi,Rakesh K Jain,Lance L Munn
Journal
PLoS Computational Biology
Published Date
2023/6/8
Professor FAQs
What is Rakesh Jain's h-index at Harvard University?
The h-index of Rakesh Jain has been 120 since 2020 and 217 in total.
What are Rakesh Jain's top articles?
The articles with the titles of
Reprogramming the Intrahepatic Cholangiocarcinoma Immune Microenvironment by Chemotherapy and CTLA-4 Blockade Enhances Anti–PD-1 Therapy
Inhibition of CXCR4 enhances the efficacy of radiotherapy in metastatic prostate cancer models
Anti-VEGF therapy improves EGFR-vIII-CAR-T cell delivery and efficacy in syngeneic glioblastoma models in mice
Desmoplasia in cervical cancer is associated with a more aggressive tumor phenotype
Mechanistic model for booster doses effectiveness in healthy, cancer, and immunosuppressed patients infected with SARS-CoV-2
Multicenter, prospective, phase II study of maintenance bevacizumab for children and adults with NF2-related schwannomatosis and progressive vestibular …
Antigen presentation deficiency, mesenchymal differentiation, and resistance to immunotherapy in the murine syngeneic CT2A tumor model
Computational simulations of tumor growth and treatment response: Benefits of high-frequency, low-dose drug regimens and concurrent vascular normalization
...
are the top articles of Rakesh Jain at Harvard University.
What is Rakesh Jain's total number of citations?
Rakesh Jain has 209,662 citations in total.