Autologous Dendritic Cells Pulsed With Tumor Lysate Antigen Vaccine and Nivolumab in Treating Patients With Recurrent Glioblastoma

Inclusion Criteria:

* PRE-SURGERY SCREENING PROCESS
* Original diagnosis of glioblastoma multiforme (GBM) confirmed by central review
* Radiographic evidence of first recurrence per Response Assessment in Neuro-Oncology (RANO) criteria confirmed by central review
* Surgically accessible, unilateral, recurrent GBM tumor for which extirpative resection, with intent to perform a gross total or near gross total resection, is indicated; a subject may be screened if he or she has had a previous biopsy and is scheduled for a subsequent gross or near gross total resection prior to commencement of other therapies
* Ability to understand and sign the tumor procurement informed consent form indicating awareness of the investigational nature of this study; the consent for tumor tissue donation may be signed by a legally authorized representative (LAR) if allowed by the institution
* Life expectancy of \>= 12 weeks
* Absolute lymphocyte count \>= 0.6 x 10\^3/mm\^3 (0.6 x 10\^9/L)
* MGMT promoter methylation status of original tumor is obtainable
* POST-SURGERY, PRIOR TO PRE-LEUKAPHERESIS
* Therapy for recurrent disease must have consisted of surgical resection extending beyond biopsy only, with the intent to achieve gross or near-total resection of the contrast-enhancing tumor mass; subjects who underwent resection confirmed beyond biopsy remain eligible for the screening process; subjects undergoing a biopsy only will be excluded; central confirmation is required before the subject can proceed to leukapheresis
* Patients with recurrent unilateral GBM, confirmed through central pathology (grade IV), without metastases, remain eligible for this protocol

  * For the purposes of this study, pathology reports for all histologically confirmed GBM includes the recognized variants of glioblastoma (small cell glioblastoma, giant cell glioblastoma, gliosarcoma, and glioblastoma with oligodendroglial components)
* All subjects must have sufficient tumor lysate protein generated from the resected tumor tissue; this determination will be made by the sponsor's contracted manufacturer and communicated to the clinical site through the sponsor or its designee; this confirmation is not required prior to the pre-leukapheresis visit, but is required before the subject can proceed to leukapheresis
* PRE-LEUKAPHERESIS EVALUATION
* Hemoglobin \> 10 g/dL (100 g/L)
* White blood cell count 3.6-11.0 x 10\^3/mm\^3 (3.6-11.0 x 10\^9/L)
* Absolute granulocyte count \>= 1.5 x 10\^3/mm\^3 (1.5 x 10\^9/L)
* Absolute lymphocyte count \>= 1.0 x 10\^3/mm\^3 (1.0 x 10\^9/L)
* Platelet count \>= 100 x 10\^3/mm\^3 (100 x 10\^9/L)
* Eligibility is maintained if these laboratory results are outside of the central laboratory's normal reference ranges or the sample ranges provided above but are not deemed clinically significant by the treating investigator
* Eligibility level of hemoglobin can be reached by transfusion; these values are determined by a central laboratory
* Serum glutamate pyruvate transaminase (SGPT) =\< 4.0 times upper limits of normal (ULN)
* Serum glutamic-oxaloacetic transaminase (SGOT) =\< 4.0 times ULN
* Alkaline phosphatase =\< 4.0 times upper limits of normal (ULN)
* Total bilirubin =\< 1.5 mg/dL (25.7 umol/L)
* Blood urea nitrogen (BUN) =\< 1.5 times ULN
* Creatinine =\< 1.5 times ULN
* Subjects must have a Karnofsky performance status (KPS) rating \>= 70 at the pre-leukapheresis visit
* PRIOR TO DAY 0
* Subjects may have received steroid therapy as part of their primary treatment; steroid treatment should be stopped or, if continued steroid use is clinically indicated, be tapered down to no more than 2 mg dexamethasone per day (or equivalent) at least 7 days prior to the first immunization
* White blood cell count \>= 2.0 x 10\^3/mm\^3 (2.0 x 10\^9/L)
* Neutrophils \>= 1.5 x 10\^3/mm\^3 (1.5 x 10\^9/L)
* Platelets \>= 100 x 10\^3/mm\^3 (100 x 10\^9/L)
* Hemoglobin \>= 9.0 g/dL (90 g/L)
* Serum creatinine =\< 1.5 x upper limit of normal (ULN)
* SGOT (aspartate aminotransferase \[AST\]) =\< 3 x ULN
* SGPT (alanine aminotransferase \[ALT\]) =\< 3 x ULN
* Total bilirubin =\< 1.5 x ULN

  * Except subjects with Gilbert's syndrome, who must have total bilirubin \< 3.0 mg/dL
* Subjects must have a KPS rating a \>= 60 at the pre-enrollment evaluation

Exclusion Criteria:

* PRE-SCREENING
* Progression on imaging based on RANO criteria within 12 weeks of conclusion of radiotherapy
* History of other prior malignancy except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or other cancers that were deemed fully resolved 5 or more years prior to surgery
* History of active, known, or suspected autoimmune or immunodeficiency disease
* Known human immunodeficiency virus (HIV)-1 or -2 or human T-cell lymphotropic virus (HTLV)-1 or -2 positivity
* Active uncontrolled infection, such as a sexually transmitted disease (STD), herpes, uncontrolled tuberculosis, malaria, etc
* Known intolerance to cyclophosphamide or other alkylating agents, or any component of any study drug
* History of active immunotherapy, including dendritic cell therapy, T cell therapy, immunization with tumor antigens in any form, any anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways or checkpoint inhibitor therapy such as ipilimumab
* History of severe infusion-related reaction to any biologics therapy
* Females who are gravid or breast-feeding
* Inability to obtain informed consent because of psychiatric or complicating medical problems
* Any known genetic cancer-susceptibility syndromes
* Any positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicative of acute or chronic infection
* AT OR AROUND SURGERY
* Bilateral or metastatic glioblastoma detected at diagnosis, during surgery, or at post-surgical magnetic resonance imaging (MRI); tumors may cross into, but not beyond, the corpus callosum
* Postoperative MRI evidence of biopsy only, without significant tumor resection, confirmed by central reviewer
* Implantation of Gliadel wafers (polifeprosan 20 with carmustine implant) at surgery
* PRE-LEUKAPHERESIS VISIT
* Positive HIV-1, -2, or HTLV-1, -2 tests
* Recipient of organ allografts
* Allergies to reagents used in this study
* Unable to stop or taper steroid treatment to no more than 2 mg of dexamethasone per day (or equivalent) prior to leukapheresis; steroid use should be stopped or tapered down to the lowest clinically acceptable dose approximately 7 days prior to leukapheresis; the leukapheresis visit must be scheduled to occur a minimum of 21 days before the projected day 0

  * It is critical to reduce steroid administration to the lowest possible dose, as steroids interfere with DCVax-L manufacturing by hampering the ability of monocytes to adhere to plastic surfaces during purification; leukapheresis should occur at least 21 days prior to the projected date of DCVax-L administration
* Inability or unwillingness to return for required visits and follow-up exams
* EXCLUSION PRIOR TO DAY 0
* Fewer than 6 doses of DCVax-L available for administration
* Continued requirement for medications that might affect immune function; the following are exceptions: nonprescription strength doses of NSAIDS, acetaminophen (paracetamol), or acetylsalicylic acid (aspirin)
* Acute infection: any active viral, bacterial, or fungal infection that requires specific therapy; antibiotic therapy must be completed at least 7 days prior to the first DCVax-L/nivolumab administration
* Fever \>= 101.5 degrees Fahrenheit (F) (38.6 degrees Celsius \[C\]); if considered possibly transient, retesting is allowed
* Unstable or severe intercurrent medical conditions
* Women of child-bearing potential (WOCBP) who are pregnant or lactating or who are not using adequate contraception and willing to do so to avoid pregnancy for 5 months after the week 20 visit
* Males who are sexually active with WOCBP and not willing to use any contraceptive method with a failure rate of less than 1% per year for 7 months after the week 20 visit
* Any dose of steroids exceeding 10 mg/day of prednisone (or equivalent) within 2 weeks prior to study drug administration