Peptide-Pulsed Dendritic Cell Vaccination in Combination With Nivolumab and Ipilimumab for the Treatment of Recurrent and/or Progressive Diffuse Hemispheric Glioma, H3 G34-mutant

Inclusion Criteria:

* Participants between the ages of 13 and 60 years with pathologically-confirmed diagnosis of (or pathology re-review consistent with) DHG will be enrolled in this study
* All participants must be undergoing clinically indicated resection surgical resection with the goal of cytoreduction
* Participants must undergo human leukocyte antigen (HLA) testing
* A female participant who has childbearing potential must have negative urine or serum pregnancy test 72 hours prior to the first dose and be willing to use adequate method of contraception for course of study and 120 days after last dose
* The participant (or legally acceptable representative if applicable) provides informed consent (and written assent from minors) for the trial
* Have unequivocal evidence for contrast-enhancing tumor progression by modified response assessment in neuro-oncology (mRANO) criteria based on MRI scan within 72 days prior to enrollment. This criterion will be reviewed by investigators prior to enrollment
* An interval of the following durations prior to enrollment:

  * At least 14 days from prior surgical resection
  * At least 7 days from prior stereotactic biopsy
  * At least 12 weeks from prior radiotherapy, unless there is unequivocal histologic confirmation of tumor progression
  * At least 23 days from prior chemotherapy
  * At least 42 days from nitrosureas
* Have sufficient archival tumor tissue confirming high-grade glioma (HGG) or variants for submission following registration. The following amount of tissue is required: 1 formalin-fixed, paraffin embedded (FFPE) tissue block (preferred) or 10 FFPE unstained slides (5 um thick)
* Have a Karnofsky Performance Status (KPS) \>= 70, if participant age \>= 16. Have a Lansky Performance Status (LPS) \>= 70, if participant age \< 16
* Absolute neutrophil count (ANC) \>= 1500/uL (within 14 days prior to start of study treatment)
* Platelets \>= 100 000/uL (microliter) (within 14 days prior to the start of study treatment)
* Hemoglobin \>= 9.0 g/dL or \>= 5.6 mmol/L (within 14 days prior to the start of study treatment)

  * Note: Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks
* Creatinine =\< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (CrCl) \>= 30 mL/min for participant with creatinine levels \> 1.5 x institutional ULN (glomerular filtration rate \[GFR\] can also be used in place of creatinine or CrCl) (within 14 days prior to the start of study treatment)

  * Note: Creatinine clearance (CrCl) should be calculated per institutional standard
* Total bilirubin =\< 1.5 x ULN OR direct bilirubin =\< ULN for participants with total bilirubin levels \> 1.5 x ULN (within 14 days prior to the start of study treatment)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 2.5 x ULN (=\< 5 x ULN for participants with liver metastases) (within 14 days prior to the start of study treatment)
* International normalized ratio (INR) OR prothrombin time (PT) =\< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants (within 14 days prior to the start of study treatment)
* Activated partial thromboplastin time (aPTT) =\< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants (within 14 days prior to the start of study treatment)

Exclusion Criteria:

* Age \< 13 years or \> 60 years
* Have had more than 2 separately-treated recurrences of the index tumor
* A woman of child-bearing potential who has a positive urine pregnancy test within 72 hours prior to enrollment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory target (e.g., CTLA-4, OX 40, CD137)
* Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to enrollment

  * Note: Participants must have recovered from all adverse events (AEs) due to previous therapies to =\< grade 1 or baseline. Participants with =\< grade 2 neuropathy may be eligible
  * Note: If participant received major surgical resection, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment
* Has received prior radiotherapy within 12 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=\< 12 weeks of radiotherapy) to non-central nervous system (CNS) disease
* Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment

  * Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent
* Has a diagnosis of immunodeficiency or is receiving chronic systemic corticosteroid therapy (dosing exceeding 1 mg/kg/day of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years

  * Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded
* Has severe hypersensitivity (\>= grade 3) to nivolumab or ipilimumab, and/or any of its excipients
* Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
* Has an active infection requiring systemic therapy
* Has a known history of hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known active hepatitis C virus (HCV) (defined as HCV ribonucleic acid (RNA) is detected) infection

  * Note: No testing for hepatitis B and hepatitis C is required unless mandated by local health authority
* Has a known history of active tuberculosis (bacillus tuberculosis)
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
* Kidney dysfunction precluding administration of gadolinium-based contrast
* Is pregnant or breastfeeding, or expecting to conceive within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment